Abstract
Desipramine (DMI) antagonizes and even “reverses” in rats autonomic and behavior changes of the reserpine-like syndrome elicited by reserpine and synthetic benzoquinolizines. The degree of this antagonism is related to the rate of brain norepinephrine-release and not to the degree of depletion of the monoamine. Since increasing the dose of the sedative benzoquinolizines (tetrabenazine, RO 4-1284, P-2565) enhances the rate of brain-norepinephrine-release, higher doses of the tranquilizers “paradoxically” increase in DMI-pretreated rats the score of total antagonism and the percentage of animals displaying the “reversal” phenomenon. The data are in keeping with the view that desipramine enhances the effect of “free” norepinephrine at central adrenergic effector sites.
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