Abstract
Desmethylimipramine (DMI), a major metabolite of imipramine, elicits no obvious pharmacological effects of its own but, in doses comparable to those used to treat primary depression in man, prevents the syndrome of effects produced by reserpine-like drugs in rats. In larger doses, DMI "reverses" the effects of reserpine-like drugs to a unique hyperactive state (spontaneous excitation) in which rats fail to respond to external stimuli.
DMI counteracts the reserpine syndrome by blocking the cholinergic effects through a central action and by sensitizing the action of the brain catecholamines at central adrenergic receptors. The anticholinergic action antagonizes the muscle rigidity and the increased parasympathetic output and occurs whether DMI is given before or after reserpine. The sensitization of central adrenergic sites is observed only when the rats are pretreated with DMI; this effect of DMI does not occur in animals which have been depleted of catecholamines by α-methyl-m-tyrosine. Furthermore, more, DMI counteracts reserpine sedation only if catecholamines are released rapidly by the reserpine-like compound. The importance of this rapid release is shown in studies with benzquinamide which, in DMI-treated animals, produces hyperactivity in doses that do not produce obvious sedation in normal animals and which release only 40% of brain NE.
Footnotes
- Received October 11, 1963.
- Accepted January 13, 1964.
- The Williams & Wilkins Company
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