Interactions of beta-adrenoceptor agonists and antagonists with the 5-hydroxytryptamine2 (5-HT2) receptor

The effect of beta-adrenoceptor agonists and antagonists on the binding of [3H]-spiperone in the frontal cortex of the rat has been examined to determine their possible interaction with the 5-hydroxytryptamine2 (5-HT2) receptor. Methysergide and the putative 5-HT2 antagonist, pirenperone, had IC50 values in the low nanomolar range whilst 5-HT and quipazine had micromolar IC50 values. Non-selective beta-adrenoceptor antagonists ((-)-propranolol, (-)-alprenolol) had similar IC50 values to 5-HT whilst selective (beta 1- or beta 2-)antagonists, (+)-propranolol and the beta-adrenoceptor agonists, clenbuterol and dobutamine, had values at least ten-fold higher. It is suggested that inhibition of 5-HT-mediated behaviour by non-selective beta-adrenoceptor antagonists results from their action at 5-HT2 receptors while clenbuterol does not enhance 5-HT-mediated behaviours by acting at this site.