THE INCREASE IN THE TOXICITY OF YOHIMBINE INDUCED BY IMIPRAMINE AND OTHER DRUGS IN MICE
Open Access
- 1 August 1963
- journal article
- research article
- Published by Wiley in British Journal of Pharmacology and Chemotherapy
- Vol. 21 (1), 51-66
- https://doi.org/10.1111/j.1476-5381.1963.tb01501.x
Abstract
In mice, yohimbine appears to accentuate the normal “alarm” reactions (alerting, flight) to external stimuli. Imipramine increases this effect and at the same time converts a non-lethal dose of yohimbine into a lethal one. The effect of imipramine is greatly reduced by adrenalectomy or by treatment with reserpine, syrosingopine, ganglion-blocking drugs or adrenaline antagonists acting on sympathetic β-receptors. Hypnotic, anti-convulsant or anaesthetic agents, tetrabenazine or antagonists of 5-hydroxytryptamine do not reduce the imipramine effect. A variety of drugs which, like imipramine, are known to interfere with the tissue binding of noradrenaline also increase the toxicity of yohimbine. Yohimbine significantly reduces brain noradrenaline content; adrenal catechol amines are slightly reduced. The results suggest that yohimbine releases noradrenaline from stores or nerves as a consequence of increased central sympathetic activity. Imipramine increases the actions and toxicity of yohimbine by increasing the effects of the released noradrenaline on β-receptors. The lethal effects of a high dose of yohimbine alone are not reduced by any of the treatments tested, and appear not to result from activation of sympathetic mechanisms.Keywords
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