Gyertyán István, Sághy Katalin
Department of Behavioural Pharmacology, Gedeon Richter Plc., Budapest, Hungary.
Eur J Pharmacol. 2007 Oct 31;572(2-3):171-4. doi: 10.1016/j.ejphar.2007.06.035. Epub 2007 Jun 29.
SB 277011-A (trans-N-[4-[2-(6-cyano-1,2,3,4-tetrahydroisoquinolin-2-yl)ethyl]cyclohexyl]-4-quinolinecarboxamide) and S 33084 [(3aR,9bS)-N4-(8-cyano-1,3a,4,9b-tetrahydro-3H-benzopyrano[3,4-c]pyrrole-2-yl)-butylbenzamide] were already shown to lack cataleptogenic actions. Further to that, we report that SB 277011 exerted a dose-dependent dampening on the development of haloperidol-induced catalepsy in the dose-range of 13.5-30 mg/kg p.o. while S 33084, at the dose of 0.625 mg/kg sc. significantly inhibited catalepsy induced by haloperidol; had no effect at 1.25 mg/kg, and further augmented the effect of haloperidol after 2.5 mg/kg. The compounds also produced effective inhibition when administered 2 hours after haloperidol. The results underline that dopamine D3 receptor antagonist action may have therapeutic value in the treatment of schizophrenia.
SB 277011-A（反式-N-[4-[2-(6-氰基-1,2,3,4-四氢异喹啉-2-基)乙基]环己基]-4-喹啉甲酰胺）和S 33084 [（3aR,9bS）-N-4-(8-氰基-1,3a,4,9b-四氢-3H-苯并吡喃并[3,4-c]吡咯-2-基)丁基苯甲酰胺]已被证明缺乏致僵作用。除此之外，我们报告称，SB 277011在13.5-30毫克/千克口服剂量范围内对氟哌啶醇诱导的僵住症的发展具有剂量依赖性的抑制作用，而S 33084在0.625毫克/千克皮下注射剂量时能显著抑制氟哌啶醇诱导的僵住症；在1.25毫克/千克时无作用，在2.5毫克/千克后会增强氟哌啶醇的作用。这些化合物在氟哌啶醇给药2小时后给药时也产生了有效的抑制作用。结果强调多巴胺D3受体拮抗剂作用在精神分裂症治疗中可能具有治疗价值。
