Studies on the mechanism of prazosin induced sympatho-inhibition

Intravenous administration of the α1-adrenoceptor antagonist, prazosin (3–300 μg/kg), produced a depression of sympathetic-cholinergic electrodermal responses evoked by electrical stimulation of the posterior hypothalamus in pentobarbital anesthetized cats. Pretreatment with the α2-adrenoceptor antagonists yohimbine (0.5 mg/kg) or idazoxan (0.1 mg/kg) significantly blocked the depressant effects of prazosin but had no effect on hypothalamic evoked electrodermal responses when given alone. Electrodermal responses were readily elicited in animals depleted of CNS monoamines. Monoamine depletion, however, totally abolished prazosin's depression of centrally evoked electrodermal responses. Prazosin also depressed the amplitude of electrodermal responses evoked by electrical stimulation of the cervical spinal cord in spinalized cats. In contrast to hypothalamic stimulation, yohimbine when given alone potentiated spinally evoked electrodermal responses which suggests that both excitatory and inhibitory mechanisms were being activated. Taken together these results suggest that prazosin produces its CNS sympatholytic effect by enhancing inhibition mediated by α2-adrenoceptor mechanisms and not directly by blockade of excitatory α1-adrenergic receptors in the central nervous system. A spinal cord site of action for prazosin is also implicated.