Analysis of CNS sympatho-inhibition produced by guanabenz.

Abstract

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.

• Authors: M C Koss
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 90 Issue 1 Pg. 19-27 (May 20 1983) ISSN: 0014-2999 [Print] Netherlands
• PMID: 6873176 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Guanidines
• Yohimbine
• Guanabenz
• Clonidine

Topics

• Animals
• Blood Pressure (drug effects)
• Cats
• Central Nervous System (drug effects)
• Clonidine (pharmacology)
• Dose-Response Relationship, Drug
• Electric Stimulation
• Female
• Ganglia, Sympathetic (drug effects)
• Guanabenz (pharmacology)
• Guanidines (pharmacology)
• Heart Rate (drug effects)
• Hypothalamus (physiology)
• Male
• Peripheral Nerves (physiology)
• Sympathetic Nervous System (drug effects)
• Yohimbine (pharmacology)