The antiaggressive potency of (-)-penbutolol involves both 5-HT1A and 5-HT1B receptors and beta-adrenoceptors

被引:17
作者
Sanchez, C
Arnt, J
Moltzen, EK
机构
[1] Pharmacological Research, H. Lundbeck A / S, DK-2500 Copenhagen-Valby
关键词
aggression; isolation-induced; 5-HT; (5-hydroxytryptamine; serotonin); beta-adrenoceptor; interaction; (Mouse);
D O I
10.1016/0014-2999(95)00727-X
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
The relative importance of 5-HT1A and beta-adrenergic activities in the antiaggressive effects of (-)-penbutolol was studied in male mice. (-)-Penbutolol had high affinity for 5-HT1A receptors and beta-adrenoceptors, and antagonized the 5-methoxy-N,N-dimethyltryptamine (5-MeODMT)-induced 5-HT syndrome and the 8-hydroxy-2-(di-n-propylamin)tetralin (8-OH-DPAT)-induced discriminatory stimulus in rats. (-)-Penbutolol abolished aggressive behaviour (ED(50) = 56 mu mol/kg), and reversed the antiaggressive effects of 8-OH-DPAT and 1-(3-trifluoromethylphenyl)piperazine (TFMPP) (ED(50) = 8.1 and 2.1 mu mol/kg, respectively). (N-[2-[4-(2-Methoxyphenyl)-1-piperazinyl]ethyl-N-(2-pyridinyl)cyclohexanecarboxamide (WAY 100635) reversed the antiaggressive effects of 8-OH-DPAT (ED(50) = 0.012 mu mol/kg), but did not affect the antiaggressive effects of TFMPP. The antiaggressive effect of a submaximal dose of 8-OH-DPAT was markedly potentiated by beta-adrenoceptor antagonists without 5-HT1A receptor affinity, whereas (-)-penbutolol was effective at only one dose (4.5 mu mol/kg). In conclusion, the 5-HT1A receptor antagonistic potency of (-)-penbutolol in aggressive mice is attenuated by beta-adrenoceptor-induced facilitation of serotonergic neurotransmission.
引用
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页码:1 / 8
页数:8
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