Different pharmacological interaction of clonidine and guanabenz with antidepressive drugs.
A study was made of the effect of several antidepressive drugs with different mechanisms of action on cardiovascular response induced by clonidine (CLO) or guanabenz (GUA) in anaesthetized normotensive rats. The acute pretreatment (1 mg.kg-1) with desipramine (DMI), maprotiline (MAP) and mianserin (MIA) reduced the hypotensive and bradycardiac responses induced by CLO (10 micrograms.kg-1), while only MIA prevented these central actions when elicited by GUA (30 micrograms.kg-1). Only chronic treatment with DMI reduced the hypotensive effect of CLO, but none of long-term antidepressant administrations decreased the fall in blood pressure induced by GUA. The long-term administration of DMI, MAP and MIA abolished the bradycardia from both agonists, CLO and GUA. The different pharmacological interaction of CLO and GUA with (acute or chronic) antidepressive treatments could be explained by a structural difference between the two agonists, and also by differences in localization and/or subtype of the alpha-adrenoceptors involved in their central cardiovascular effects.
Gutkind
J S
JS
Cátedra de Farmacología, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Argentina.
Enero
M A
MA
D000818:Animals; D000928:Antidepressive Agents / Q000008:administration & dosage*; D001794:Blood Pressure / Q000187:drug effects; D002319:Cardiovascular System / Q000187:drug effects*; D003000:Clonidine / Q000008:administration & dosage*; D004347:Drug Interactions; D005260:Female; D006143:Guanabenz / Q000008:administration & dosage*; D006146:Guanidines / Q000008:administration & dosage*; D006339:Heart Rate / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects
D000928:Antidepressive Agents; D006146:Guanidines; D011942:Receptors, Adrenergic, alpha; D006143:Guanabenz; D003000:Clonidine