Potentiation of fluoxetine-induced penile erections by combined blockade of 5-HT1A and 5-HT1B receptors |
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| Affiliation: | 1. Department of Clinical Biochemistry, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran;2. Department of Medicine, University of Alberta, Edmonton, AB, Canada;3. Legal Medicine Research Center, Legal Medicine Organization, Tabriz, Iran;4. School of Health and Nutrition, Tabriz University of Medical Sciences, Tabriz, Iran;2. Division of Nephrology, Department of Medcine, New York Medical College, Valhalla, NY |
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| Abstract: | The serotonin reuptake inhibitor, fluoxetine (10.0 mg/kg, s.c.), elicited penile erections in rats. Selective blockade of 5-HT1A autoreceptors with WAY 100,635 ((N-{2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl}-N-(2-pyridinyl) cyclo-hexanecarboxamide) (0.16 mg/kg, s.c.), or of 5-HT1B autoreceptors with GR 127,935 (N-[4-methoxy-3-(4-methylpiperazin-1-yl)phenyl]-2′-methyl-4′-(5-methyl-1,2,4-oxadiazol-3-yl)biphenyl-4-carboxamide) (2.5 mg/kg, s.c.), slightly (1.5- to 2-fold) increased fluoxetine-induced penile erections. However, conjoint administration of WAY 100,635 and GR 127,935 markedly (5-fold) potentiated induction of penile erections by fluoxetine. Penile erections were abolished by the novel 5-HT2C receptor antagonist, SB 206,553 (5 methyl-1-(3-pyridil-carbamoyl)-1,2,3,5-tetrahydropyrrolo[2,3-f]indole). These data provide functional evidence for redundancy in autoreceptor control of 5-HT release. Combined blockade of 5-HT1A and 5-HT1B autoreceptors markedly enhances the actions of serotonin reuptake inhibitors. © 1997 Elsevier Science B.V. All rights reserved. |
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