扎考必利

扎考必利（英語：Zacopride），或譯為查可必利，是5-HT₃受體的有效拮抗劑^[1]和5-HT₄受體的激動劑。^[2]它在動物模型中具有抗焦慮^[3]和促智作用，^[4]其中(R)-(+)-對映體是更活躍的形式。^[5]它還具有止吐^[6]和促呼吸作用，在動物研究中既能減少睡眠呼吸暫停，^[7]又能逆轉阿片類藥物引起的呼吸抑制。^[8]早期的動物試驗還表明，給予扎考必利可以減少對乙醇的偏好和消耗。^[9]

扎考必利

臨床資料
ATC碼	未分配
識別資訊
IUPAC命名法 4-amino-5-chloro-2-methoxy-N-(quinuclidin-3-yl)benzamide
CAS號	90182-92-6  Y
PubChem CID	108182
IUPHAR/BPS	245
ChemSpider	97262 N
UNII	9GN3OT4156
ChEMBL	ChEMBL18041 N
CompTox Dashboard（英語：CompTox Chemicals Dashboard） (EPA)	DTXSID1048251
化學資訊
化學式	C15H20ClN3O2
摩爾質量	309.79 g·mol−1
3D模型（JSmol（英語：JSmol））	交互式圖像
SMILES COC1=CC(=C(C=C1C(=O)NC2CN3CCC2CC3)Cl)N
InChI InChI=1S/C15H20ClN3O2/c1-21-14-7-12(17)11(16)6-10(14)15(20)18-13-8-19-4-2-9(13)3-5-19/h6-7,9,13H,2-5,8,17H2,1H3,(H,18,20) N Key:FEROPKNOYKURCJ-UHFFFAOYSA-N N

發現扎考必利在400微克的劑量下顯著增加人類受試者的醛固酮水平達180分鐘。人們認為這是通過刺激腎上腺上的5-HT₄受體來實現的。扎考必利在體外應用於人腎上腺時也能刺激醛固酮分泌。腎素、促腎上腺皮質激素或皮質醇水平未觀察到顯著變化。^[2]

扎考必利已在治療精神分裂症的臨床試驗中進行了測試，但未獲成功。^[10]

參考資料

1. Smith WW, Sancilio LF, Owera-Atepo JB, Naylor RJ, Lambert L. Zacopride, a potent 5-HT3 antagonist. The Journal of Pharmacy and Pharmacology. April 1988, 40 (4): 301–2. PMID 2900319. S2CID 32862252. doi:10.1111/j.2042-7158.1988.tb05253.x.
2. Lefebvre H, Contesse V, Delarue C, Soubrane C, Legrand A, Kuhn JM, et al. Effect of the serotonin-4 receptor agonist zacopride on aldosterone secretion from the human adrenal cortex: in vivo and in vitro studies. The Journal of Clinical Endocrinology and Metabolism. December 1993, 77 (6): 1662–6. PMID 8263156. doi:10.1210/jcem.77.6.8263156.
3. Costall B, Domeney AM, Gerrard PA, Kelly ME, Naylor RJ. Zacopride: anxiolytic profile in rodent and primate models of anxiety. The Journal of Pharmacy and Pharmacology. April 1988, 40 (4): 302–5. PMID 2900320. S2CID 1083706. doi:10.1111/j.2042-7158.1988.tb05254.x.
4. Fontana DJ, Daniels SE, Eglen RM, Wong EH. Stereoselective effects of (R)- and (S)-zacopride on cognitive performance in a spatial navigation task in rats. Neuropharmacology. March 1996, 35 (3): 321–7. PMID 8783207. S2CID 12818436. doi:10.1016/0028-3908(96)00191-8.
5. Young R, Johnson DN. Anxiolytic-like activity of R(+)- and S(-)-zacopride in mice. European Journal of Pharmacology. August 1991, 201 (2–3): 151–5. PMID 1686755. doi:10.1016/0014-2999(91)90338-Q.
6. Yamakuni H, Nakayama H, Matsui S, Imazumi K, Matsuo M, Mutoh S. Inhibitory effect of zacopride on Cisplatin-induced delayed emesis in ferrets. Journal of Pharmacological Sciences. May 2006, 101 (1): 99–102. PMID 16651699. doi:10.1254/jphs.SCJ05007X .
7. Carley DW, Depoortere H, Radulovacki M. R-zacopride, a 5-HT3 antagonist/5-HT4 agonist, reduces sleep apneas in rats. Pharmacology, Biochemistry, and Behavior. 2001, 69 (1–2): 283–9. PMID 11420096. S2CID 11848748. doi:10.1016/S0091-3057(01)00535-4.
8. Meyer LC, Fuller A, Mitchell D. Zacopride and 8-OH-DPAT reverse opioid-induced respiratory depression and hypoxia but not catatonic immobilization in goats. American Journal of Physiology. Regulatory, Integrative and Comparative Physiology. February 2006, 290 (2): R405–13. PMID 16166206. S2CID 224414. doi:10.1152/ajpregu.00440.2005.
9. Knapp DJ, Pohorecky LA. Zacopride, a 5-HT3 receptor antagonist, reduces voluntary ethanol consumption in rats. Pharmacology, Biochemistry, and Behavior. April 1992, 41 (4): 847–50. PMID 1594653. S2CID 45436887. doi:10.1016/0091-3057(92)90237-A.
10. Newcomer JW, Faustman WO, Zipursky RB, Csernansky JG. Zacopride in schizophrenia: a single-blind serotonin type 3 antagonist trial. Archives of General Psychiatry. September 1992, 49 (9): 751–2. PMID 1514881. doi:10.1001/archpsyc.1992.01820090079013.