A-77636

A-77636
	IUPAC名 (1R,3S)-3-(1-Adamantyl)-1-(aminomethyl)-3,4-dihydro-1H-isochromene-5,6-diol
識別情報
CAS登録番号	778546-51-3 , 145307-34-2 (HCl)
PubChem	66037039951033 (HCl)
ChemSpider	5036017
ChEMBL	CHEMBL313530
	SMILES Oc1ccc2c(c1O)C[C@H](O[C@H]2CN)C35CC4CC(C3)CC(C4)C5;
	InChI InChI=1S/C20H27NO3/c21-10-17-14-1-2-16(22)19(23)15(14)6-18(24-17)20-7-11-3-12(8-20)5-13(4-11)9-20/h1-2,11-13,17-18,22-23H,3-10,21H2/t11?,12?,13?,17-,18-,20?/m0/s1 Key: QLJOSZATCBCBDR-DFKUFRTHSA-N ; InChI=1/C20H27NO3/c21-10-17-14-1-2-16(22)19(23)15(14)6-18(24-17)20-7-11-3-12(8-20)5-13(4-11)9-20/h1-2,11-13,17-18,22-23H,3-10,21H2/t11?,12?,13?,17-,18-,20?/m0/s1 Key: QLJOSZATCBCBDR-DFKUFRTHBM;
特性
化学式	C20H27NO3
モル質量	329.43 g mol−1
精密質量	329.199093735 g mol-1
	特記なき場合、データは常温 (25 °C)・常圧 (100 kPa) におけるものである。

A-77636は、D₁受容体のフルアゴニストとして選択的に作用する合成薬である^[2]。向知性薬、食欲減退薬であり、動物実験では抗パーキンソン病薬としての効果が得られている^[3]^[4]^[5]^[6]^[7]。しかしながら、その高い有効性と長期作用によりD₁受容体がダウンレギュレーションとタキフィラキシーを引き起こす^[8]^[9]^[10]。SKF-82958などの他のD₁フルアゴニストとは異なり場所し好性を生成しない^[11]。A-77636は動物実験において部分的にコカインと置換され、中毒治療の可能性代替薬としての使用が推奨されており^[12]、これは脳内D₁受容体の役割の研究における使用がよく知られている^[13]^[14]^[15]。

出典[編集]

^ CID 6603703 - PubChem
^ Kebabian JW, Britton DR, DeNinno MP, Perner R, Smith L, Jenner P, Schoenleber R, Williams M (December 1992). “A-77636: a potent and selective dopamine D1 receptor agonist with antiparkinsonian activity in marmosets”. European Journal of Pharmacology 229 (2-3): 203–9. doi:10.1016/0014-2999(92)90556-J. PMID 1362704.
^ Asin KE, Nikkel AL, Wirtshafter D (February 1994). “Repeated D1 receptor agonist treatment blocks cocaine-induced locomotor activity and c-fos expression”. Brain Research 637 (1-2): 342–4. doi:10.1016/0006-8993(94)91258-0. PMID 7910104.
^ Ranaldi R, Beninger RJ (July 1994). “The effects of systemic and intracerebral injections of D1 and D2 agonists on brain stimulation reward”. Brain Research 651 (1-2): 283–92. doi:10.1016/0006-8993(94)90708-0. PMID 7922577.
^ Grondin R, Bédard PJ, Britton DR, Shiosaki K (August 1997). “Potential therapeutic use of the selective dopamine D1 receptor agonist, A-86929: an acute study in parkinsonian levodopa-primed monkeys”. Neurology 49 (2): 421–6. PMID 9270571.
^ Cai JX, Arnsten AF (October 1997). “Dose-dependent effects of the dopamine D1 receptor agonists A77636 or SKF81297 on spatial working memory in aged monkeys”. The Journal of Pharmacology and Experimental Therapeutics 283 (1): 183–9. PMID 9336323.
^ Cooper SJ, Al-Naser HA, Clifton PG (February 2006). “The anorectic effect of the selective dopamine D1-receptor agonist A-77636 determined by meal pattern analysis in free-feeding rats”. European Journal of Pharmacology 532 (3): 253–7. doi:10.1016/j.ejphar.2005.11.046. PMID 16478622.
^ Lin CW, Bianchi BR, Miller TR, Stashko MA, Wang SS, Curzon P, Bednarz L, Asin KE, Britton DR (March 1996). “Persistent activation of the dopamine D1 receptor contributes to prolonged receptor desensitization: studies with A-77636”. The Journal of Pharmacology and Experimental Therapeutics 276 (3): 1022–9. PMID 8786531.
^ Saklayen SS, Mabrouk OS, Pehek EA (October 2004). “Negative feedback regulation of nigrostriatal dopamine release: mediation by striatal D1 receptors”. The Journal of Pharmacology and Experimental Therapeutics 311 (1): 342–8. doi:10.1124/jpet.104.067991. PMID 15175419.
^ Ryman-Rasmussen JP, Griffith A, Oloff S, Vaidehi N, Brown JT, Goddard WA, Mailman RB (February 2007). “Functional selectivity of dopamine D1 receptor agonists in regulating the fate of internalized receptors”. Neuropharmacology 52 (2): 562–75. doi:10.1016/j.neuropharm.2006.08.028. PMC 1855220. PMID 17067639.
^ Graham DL, Hoppenot R, Hendryx A, Self DW (April 2007). “Differential ability of D1 and D2 dopamine receptor agonists to induce and modulate expression and reinstatement of cocaine place preference in rats”. Psychopharmacology 191 (3): 719–30. doi:10.1007/s00213-006-0473-5. PMID 16835769.
^ Chausmer AL, Katz JL (January 2002). “Comparison of interactions of D1-like agonists, SKF 81297, SKF 82958 and A-77636, with cocaine: locomotor activity and drug discrimination studies in rodents”. Psychopharmacology 159 (2): 145–53. doi:10.1007/s002130100896. PMID 11862342.
^ Acquas E, Wilson C, Fibiger HC (April 1997). “Nonstriatal dopamine D1 receptors regulate striatal acetylcholine release in vivo”. The Journal of Pharmacology and Experimental Therapeutics 281 (1): 360–8. PMID 9103518.
^ Ruskin DN, Rawji SS, Walters JR (July 1998). “Effects of full D1 dopamine receptor agonists on firing rates in the globus pallidus and substantia nigra pars compacta in vivo: tests for D1 receptor selectivity and comparisons to the partial agonist SKF 38393”. The Journal of Pharmacology and Experimental Therapeutics 286 (1): 272–81. PMID 9655869.
^ Bubser M, Fadel JR, Jackson LL, Meador-Woodruff JH, Jing D, Deutch AY (June 2005). “Dopaminergic regulation of orexin neurons”. The European Journal of Neuroscience 21 (11): 2993–3001. doi:10.1111/j.1460-9568.2005.04121.x. PMID 15978010.

[1] CID 6603703 - PubChem

[pmid1362704-2] Kebabian JW, Britton DR, DeNinno MP, Perner R, Smith L, Jenner P, Schoenleber R, Williams M (December 1992). “A-77636: a potent and selective dopamine D1 receptor agonist with antiparkinsonian activity in marmosets”. European Journal of Pharmacology 229 (2-3): 203–9. doi:10.1016/0014-2999(92)90556-J. PMID 1362704.

[pmid7910104-3] Asin KE, Nikkel AL, Wirtshafter D (February 1994). “Repeated D1 receptor agonist treatment blocks cocaine-induced locomotor activity and c-fos expression”. Brain Research 637 (1-2): 342–4. doi:10.1016/0006-8993(94)91258-0. PMID 7910104.

[pmid7922577-4] Ranaldi R, Beninger RJ (July 1994). “The effects of systemic and intracerebral injections of D1 and D2 agonists on brain stimulation reward”. Brain Research 651 (1-2): 283–92. doi:10.1016/0006-8993(94)90708-0. PMID 7922577.

[pmid9270571-5] Grondin R, Bédard PJ, Britton DR, Shiosaki K (August 1997). “Potential therapeutic use of the selective dopamine D1 receptor agonist, A-86929: an acute study in parkinsonian levodopa-primed monkeys”. Neurology 49 (2): 421–6. PMID 9270571.

[pmid9336323-6] Cai JX, Arnsten AF (October 1997). “Dose-dependent effects of the dopamine D1 receptor agonists A77636 or SKF81297 on spatial working memory in aged monkeys”. The Journal of Pharmacology and Experimental Therapeutics 283 (1): 183–9. PMID 9336323.

[pmid16478622-7] Cooper SJ, Al-Naser HA, Clifton PG (February 2006). “The anorectic effect of the selective dopamine D1-receptor agonist A-77636 determined by meal pattern analysis in free-feeding rats”. European Journal of Pharmacology 532 (3): 253–7. doi:10.1016/j.ejphar.2005.11.046. PMID 16478622.

[pmid8786531-8] Lin CW, Bianchi BR, Miller TR, Stashko MA, Wang SS, Curzon P, Bednarz L, Asin KE, Britton DR (March 1996). “Persistent activation of the dopamine D1 receptor contributes to prolonged receptor desensitization: studies with A-77636”. The Journal of Pharmacology and Experimental Therapeutics 276 (3): 1022–9. PMID 8786531.

[pmid15175419-9] Saklayen SS, Mabrouk OS, Pehek EA (October 2004). “Negative feedback regulation of nigrostriatal dopamine release: mediation by striatal D1 receptors”. The Journal of Pharmacology and Experimental Therapeutics 311 (1): 342–8. doi:10.1124/jpet.104.067991. PMID 15175419.

[pmid17067639-10] Ryman-Rasmussen JP, Griffith A, Oloff S, Vaidehi N, Brown JT, Goddard WA, Mailman RB (February 2007). “Functional selectivity of dopamine D1 receptor agonists in regulating the fate of internalized receptors”. Neuropharmacology 52 (2): 562–75. doi:10.1016/j.neuropharm.2006.08.028. PMC 1855220. PMID 17067639.

[pmid16835769-11] Graham DL, Hoppenot R, Hendryx A, Self DW (April 2007). “Differential ability of D1 and D2 dopamine receptor agonists to induce and modulate expression and reinstatement of cocaine place preference in rats”. Psychopharmacology 191 (3): 719–30. doi:10.1007/s00213-006-0473-5. PMID 16835769.

[pmid11862342-12] Chausmer AL, Katz JL (January 2002). “Comparison of interactions of D1-like agonists, SKF 81297, SKF 82958 and A-77636, with cocaine: locomotor activity and drug discrimination studies in rodents”. Psychopharmacology 159 (2): 145–53. doi:10.1007/s002130100896. PMID 11862342.

[pmid9103518-13] Acquas E, Wilson C, Fibiger HC (April 1997). “Nonstriatal dopamine D1 receptors regulate striatal acetylcholine release in vivo”. The Journal of Pharmacology and Experimental Therapeutics 281 (1): 360–8. PMID 9103518.

[pmid9655869-14] Ruskin DN, Rawji SS, Walters JR (July 1998). “Effects of full D1 dopamine receptor agonists on firing rates in the globus pallidus and substantia nigra pars compacta in vivo: tests for D1 receptor selectivity and comparisons to the partial agonist SKF 38393”. The Journal of Pharmacology and Experimental Therapeutics 286 (1): 272–81. PMID 9655869.

[pmid15978010-15] Bubser M, Fadel JR, Jackson LL, Meador-Woodruff JH, Jing D, Deutch AY (June 2005). “Dopaminergic regulation of orexin neurons”. The European Journal of Neuroscience 21 (11): 2993–3001. doi:10.1111/j.1460-9568.2005.04121.x. PMID 15978010.

[1]

[2]

[3]

[4]

[5]

[6]

[7]

[8]

[9]

[10]

[11]

[12]

[13]

[14]

[15]