Studies on the mechanism of prazosin induced sympatho-inhibition.
Intravenous administration of the alpha 1-adrenoceptor antagonist, prazosin (3-300 micrograms/kg), produced a depression of sympathetic-cholinergic electrodermal responses evoked by electrical stimulation of the posterior hypothalamus in pentobarbital anesthetized cats. Pretreatment with the alpha 2-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 alpha 2-adrenoceptor mechanisms and not directly by blockade of excitatory alpha 1-adrenergic receptors in the central nervous system. A spinal cord site of action for prazosin is also implicated.
Ito
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Department of Pharmacology, University of Oklahoma Health Sciences Center, Oklahoma City 73190.
Hey
J A
JA
Koss
M C
MC
D000320:Adrenergic Fibers / Q000187:drug effects; D000588:Amines / Q000378:metabolism; D000818:Animals; D002415:Cats; D002490:Central Nervous System / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D004146:Dioxanes / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D005071:Evoked Potentials / Q000187:drug effects; D007034:Hypothalamus, Posterior / Q000502:physiology; D019329:Idazoxan; D011224:Prazosin / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000502:physiology; D013116:Spinal Cord / Q000187:drug effects; D015016:Yohimbine / Q000008:administration & dosage
D000588:Amines; D004146:Dioxanes; D011942:Receptors, Adrenergic, alpha; D015016:Yohimbine; D011224:Prazosin; D019329:Idazoxan