Modification of reserpine induced rigidity by dopaminergic and alpha-adrenergic drugs

Previous studies have reported that a variety of drugs are effective in preventing reserpine-induced hypertonus, including dopamine agonists and alpha-adrenergic antagonists. The purpose of this study was to use a quantitative measure of hindlimb muscle tone to evaluate the relative efficacy of various drugs with known pharmacologic actions on dopaminergic and adrenergic receptors. The results show that adrenergic antagonists (yohimbine, thymoxamine, phentolamine, RS 21361) were the most effective in protecting against the effect of reserpine. Along with the dopamine precursor, 1-DOPA, these drugs were not only effective but also they produced no muscle relaxation in non-reserpinized rats. Although dopamine agonists (apomorphine, lisuride, bromocriptine) also protected against reserpine-induced rigidity, these drugs also produced muscle relaxation in non-reserpinized rats. A variety of drugs with alpha adrenergic agonist, beta adrenergic antagonist, dopamine antagonist and antihistamine activity did not alter the reserpine-induced rigidity despite generalized muscle relaxant effects with some of these. The results show that alpha adrenergic antagonists are the most selective agents in preventing reserpine-induced rigidity and suggest that alpha-2 receptors primarily mediate this effect.