Archives internationales de pharmacodynamie et de thérapie
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Arch Int Pharmacodyn Ther · May 1982
Effects of alpha-adrenoceptor antagonists administered intraventricularly on central hypotensive action of clonidine and on central hypertensive action of methoxamine in rabbits.
In urethane-anesthetized rabbits blood pressure was lowered by intraventricular clonidine (30 microgram) and increased by intraventricular methoxamine (1 mg). Clonidine is well known to cause hypotension by acting on central alpha-adrenoceptors. The hypertensive effect of intraventricular methoxamine was not observed in cord-sectioned rabbits, in guanethidine-treated adrenalectomized rabbits and in phentolamine-treated rabbits, indicating the effect was central in origin. ⋯ Pretreatment with 2 mg of labetalol inhibited the methoxamine effect but was ineffective against clonidine. Pretreatment with 500 microgram of phentolamine was effective in antagonizing the clonidine effect but twice the dose was needed to inhibit the methoxamine effect. From the findings that the hypertensive effect of methoxamine and the hypotensive effect of clonidine were inhibited differently by various alpha-adrenoceptor antagonists and that the selectivity of these antagonists for the methoxamine and clonidine effect is similar, respectively, to that for alpha 1- and alpha 2-adrenoceptors in the peripheral tissues, we concluded that the methoxamine hypertension and the clonidine hypotension are due to the stimulation of alpha 1- and alpha 2- adrenoceptors in the brain, respectively.