Analysis of CNS sympatho-inhibition produced by guanabenz.
The effects of guanabenz on several autonomic systems were observed in vagotomized, anesthetized cats with the aim of determining, in a quantitative sense, the degree to which guanabenz produces a clonidine-like central nervous system action. Guanabenz given as a single dose (50 micrograms/kg i.v.) produced a transient hypertension associated with a more sustained bradycardia and depression of centrally (hypothalamic) evoked electrodermal responses (EDR). Increasing cumulative doses of guanabenz (3-1000 micrograms/kg i.v.) also resulted in a dose-related depression of EDR amplitude, transient hypertension followed by hypotension, sustained bradycardia, and mydriasis. All responses were antagonized by pretreatment with yohimbine (0.5 mg/kg i.v.). The ED50 for depression of the centrally evoked EDR was in the range of 50-100 micrograms/kg i.v. in the non-pretreated preparations. Guanabenz (100 micrograms/kg i.v.) was shown to be devoid of significant ganglionic blocking properties. These experiments suggest that guanabenz acts like clonidine in the CNS and that an alpha 2-adrenergic inhibitory mechanism is involved in its myriad of central autonomic effects.
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002415:Cats; D002490:Central Nervous System / Q000187:drug effects*; D003000:Clonidine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D005260:Female; D005728:Ganglia, Sympathetic / Q000187:drug effects; D006143:Guanabenz / Q000494:pharmacology*; D006146:Guanidines / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects; D007031:Hypothalamus / Q000502:physiology; D008297:Male; D010525:Peripheral Nerves / Q000502:physiology; D013564:Sympathetic Nervous System / Q000187:drug effects*; D015016:Yohimbine / Q000494:pharmacology
D006146:Guanidines; D015016:Yohimbine; D006143:Guanabenz; D003000:Clonidine