Sympatholytic action of yohimbine mediated by 5-HT1A receptors.
The present study determined the mechanism by which yohimbine inhibits sympathetic nerve activity in the anesthetized cat. Low i.v. doses of yohimbine increased inferior cardiac nerve discharge as a result of the alpha 2-adrenoceptor antagonist properties of the drug. Higher doses of yohimbine (0.8-1.6 mg/kg) inhibited sympathetic nerve discharge. The inhibition of nerve activity was reversed by i.v. administration of the 5HT1A receptor antagonist spiperone. Similarly we have previously observed spiperone reversal of the sympatholytic effects of the 5-HT1A agonist 8-OH-DPAT (8-hydroxy-2-(di-n-propylamino)tetralin) but failed to affect nerve activity when given alone. Spiperone failed to reverse the sympatholytic effect of clonidine. These data indicate that high doses of yohimbine inhibit sympathetic nerve activity via a 5HT1A agonist action.
McCall
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Cardiovascular Disease Research, Upjohn Company, Kalamazoo, MI 49001.
Harris
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King
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D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D000317:Adrenergic alpha-Antagonists; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D002415:Cats; D003000:Clonidine / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D007275:Injections, Intravenous; D011985:Receptors, Serotonin / Q000502:physiology*; D013134:Spiperone / Q000494:pharmacology; D013564:Sympathetic Nervous System / Q000187:drug effects* / Q000502:physiology; D013764:Tetrahydronaphthalenes / Q000494:pharmacology; D015016:Yohimbine / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*
D000317:Adrenergic alpha-Antagonists; D011985:Receptors, Serotonin; D013764:Tetrahydronaphthalenes; D015016:Yohimbine; D013134:Spiperone; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D003000:Clonidine