Treatment with clorgyline and pargyline differentially decreases clonidine-induced hypotension and bradycardia |
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Authors: | Jorge S Gutkind Maria Amelia Enero |
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Institution: | (1) Cátedra de Farmacología, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Junín 956-5°Piso, RA-1113 Buenos Aires, Argentina;(2) Instituto de Investigaciones Farmacológicas, CONICET, Junín 956-5° Piso, RA-1113 Buenos Aires, Argentina |
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Abstract: | Summary A study was made of the effects of acute and chronic treatment with monoamine-oxidase (MAO) inhibitiors on the peripheral and central cardiovascular response induced by clonidine in anaesthetized normotensive rats. Clonidine (30 nmoles · kg–1 i.v.) produced a biphasic change in mean blood pressure; an initial transient increase was followed by a prolonged hypotensive effect, coinciding with the maximal bradycardia. Twenty-four hours after acute (single) or chronic (daily for 7 days) administration of MAO inhibitors (pargyline 10 mg · kg–1 SC or clorgyline 0.3 mg · kg–1 SC) there was no effect either on the basal cardiovascular parameters or on the initial pressor response induced by clonidine. Chronic but not acute treatment with clorgyline, an inhibitor of type A MAO, greatly decreased the hypotension and bradycardia induced by clonidine for as long as 5 days after its discontinuation. On the other hand, after chronic administration of pargyline (10 mg · kg–1), a preferential type B MAO inhibitor, the hypotension and bradycardia caused by clonidine were differently affected. There was a reduction in the bradycardia up to the third day following the discontinuation of pargyline, whereas the hypotensive response induced by clonidine was only attenuated for 24 h and unaffected with a lower dose of pargyline (0.3 mg · kg–1).It is concluded that chronic administration of the type A MAO inhibitor, clorgyline, attenuates the central responses to clonidine through the reduction in sensitivity of brain -adrenoceptors. Pargyline, that preferentially inhibits type B MAO, reduces only the bradycardia induced by clonidine. This result may indicate a different modulation of the receptors involved in this response to clonidine. |
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Keywords: | Monoamine oxidase Pargyline Clorgyline Cardiovascular response Clonidine |
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