Involvement of beta 2-adrenoceptor blockade and 5-hydroxytryptamine mechanism in inhibition of harmaline-induced tremors in rats.

Specific beta 1- and beta 2-adrenoceptor antagonists, acebutolol and butoxamine respectively were used to investigate the involvement of blockade of these receptors in the inhibition of harmaline-induced tremors. Both agents produced an antitremor effect in a dose-dependent manner, with butoxamine showing greater potency than acebutolol. The dose of isoprenaline (0.1 mg/kg) that markedly reduced the effect of butoxamine did not alter the effect of acebutolol, suggesting that antagonism of peripheral beta 1-adrenoceptor was not responsible for the antitremor action of acebutolol and that blockade of peripheral beta 2-receptors is involved to a great extent in the inhibition of tremors by butoxamine. The effect of acebutolol was unaltered in rats pretreated with 5-hydroxytryptophan and p-chlorophenylalanine, which on the other hand produced potentiation and a partial reduction respectively of the action of butoxamine. It appears, therefore, that butoxamine also acts centrally in association with the 5-HT system and that this action is relatively weaker than the peripheral action. The dual action on two sites may account for the potent antitremor action of butoxamine.