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Journal of Pharmacology And Experimental Therapeutics, Vol. 144, Issue 3, 405-414, 1964
Copyright © 1964 by American Society for Pharmacology and Experimental Therapeutics

MODE OF ACTION OF IMIPRAMINE ANID 5-(3'-METHYLAMINOPROPYLIDEN)-DIBENZO[a,e]CYCLOHEPTA[1,3,5]TRIEN HYDROCHLORIDE (RO 4-6011), A NEW ANTIDEPRESSANT DRUG, ON PERIPHERAL ADRENERGIC MECHANISMS

H. Thoenen 1, A. Huerlimann 1, and W. Haefely 1

1 Department of Experimental Medicine, F. Hoffmann-La Roche & Co. Led., Basle, Switzerland

The effect of imipramine and Ro 4-6011 was studied a) on the contractile response and on the norepinephrine output following sympathetic nerve stimulation in the isolated perfused spleen of the cat and b) on the inactivation of intravenously injected norepinephrine in spinal cats.

Both drugs increased the norepinephrine output resulting from sympathetic stimulation in the isolated perfused spleen and delayed the inactivation of injected norepinephrine in spinal cats. These effects are most likely due to inhibition of norepinephrine uptake into storage sites.

In low concentrations both imipramine and Ro 4-6011 increased the contractile response of the spleen following sympathetic stimulation. At higher concentrations an adrenolytic effect appeared : while the duration of the contraction and the norepinephrine output remained increased, the intensity of the response was reduced. Thus imipramine and Ro 4-6011 act on adrenergic receptors as well as on the storage sites for norepinephrine. Whether the norepinephrine potentiation or the adrenolytic effect prevails depends on the concentration of the drugs and the regional importance of norepinephrine uptake into storage sites for the termination of its pharmacological effect.

Submitted on November 8, 1963
Accepted on January 6, 1964




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Copyright © 1964 by the American Society for Pharmacology and Experimental Therapeutics.