Behavioral effect of beta-blocking drugs resulting from the stimulation or the blockade of serotonergic 5-HT1B receptors.
The present study was aimed at determining the relative potency of various beta-blocking drugs as agonists or antagonists at 5-HT1B receptors. The behavioral model used (increase in escape attempts of isolated mice) has been previously shown to be exclusively responsive to 5-HT1B agonists such as 1-3-(trifluoromethyl) phenylpiperazine (TFMPP). Beta-blocking drugs acted in three different ways: they were either inactive, or acted as agonists or as antagonists at 5-HT1B receptors. The specific beta-blocking drugs: atenolol and betaxolol (beta-1) and ICI 118,551 (beta-2) were inactive by themselves and in interaction with TFMPP. The mixed beta-1 beta-2 blocking drug 1-penbutolol, (but not d-penbutolol), inactive alone, behaved as an antagonist: it impaired in a dose-dependent way the effect of TFMPP. (+/-)Pindolol and (-)pindolol was inactive. None of the (-), (+), or (+/-)pindolol was able to impair TFMPP effect. The increase in escape attempts induced by (+/-)pindolol was antagonized with 1-penbutolol or after a specific desensitization. Cyanopindolol and S-tertatolol (but not R-tertatolol) acted as agonists. SDZ 21009 was inactive as agonist or antagonist. It may be concluded that all beta-blocking drugs are not equivalent regarding their effect at 5-HT1B receptors. L-penbutolol was the only drug acting as an antagonist.
INSERM U.26, Unité de Neurotoxicologie, Hôpital Fernand Widal, France.
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H
Frances
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Monier
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Debray
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004361:Drug Tolerance; D008297:Male; D008719:Methiothepin / Q000494:pharmacology; D051379:Mice; D010879:Piperazines / Q000494:pharmacology; D011985:Receptors, Serotonin / Q000187:drug effects*; D012702:Serotonin Antagonists / Q000494:pharmacology*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D012934:Social Isolation
D000319:Adrenergic beta-Antagonists; D010879:Piperazines; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; C018406:1-(3-trifluoromethylphenyl)piperazine; D008719:Methiothepin