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.