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 var ious beta-blocking drugs as agonists or antagonists at 5-HT1B receptor s. 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 inacti ve, or acted as agonists or as antagonists at 5-HT1B receptors. The sp ecific beta-blocking drugs: atenolol and betaxolol (beta-1) and ICI 11 8 551 (beta-2) were inactive by themselves and in interaction with TFM PP. The mixed beta-1 beta-2 blocking drug 1-penbutolol, (but not d-pen butolol), inactive alone, behaved as an antagonist: it impaired in a d ose-dependent way the effect of TFMPP. (+/-)Pindolol and (-)pindolol a cted as agonists; (+)pindolol was inactive. None of the (-), (+), or ( +/-)pindolol was able to impair TFMPP effect. The increase in escape a ttempts induced by (+/-)pindolol was antagonized with l-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 n ot equivalent regarding their effect at 5-HT1B receptors. L-penbutolol was the only drug acting as an antagonist.