DIFFERENTIAL EFFECTS OF ISOMERS OF TETRAMISOLE ON ADRENERGIC NEUROTRANSMISSION IN CUTANEOUS VEINS OF DOG

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  • 1 January 1977
    • journal article
    • research article
    • Vol. 200  (1) , 127-140
Abstract
Clinical observations indicate that dexamisole and levamisole, the isomers of tetramisole, cause mood elevation. Their effects on smooth muscle cells and adrenergic nerves were investigated in strips of dogs'' saphenous veins. Dexamisole (2.5 .times. 10-6 to 4 .times. 10-5 M) augmented the contractile response to norepinephrine but depressed that to tyramine; cocaine inhibited augmentation of norepinephrine response. Levamisole (10-5 M) did not alter the response to norepinephrine but augmented that to tyramine. At 1.6 .times. 10-4 M dexamisole, more than levamisole, depressed responses to norepinephrine, tyramine and acetylcholine. Activation by K+ ions was not affected by the isomers. Preparations, incubated with 3H-norepinephrine, were mounted for superfusion, tension recording and determination of 3H-norepinephrine and metabolites in the superfusate. Dexamisole and levamisole augmented the 3H-norepinephrine overflow during nerve stimulation; levamisole decreased the efflux of deaminated metabolites. During tyramine-induced contractions, dexamisole depressed and levamisole augmented the efflux of 3H-norepinephrine; they reduced the appearance of metabolites. Increases in 3H-norepinephrine caused by the isomers during nerve stimulation were not seen after phenoxybenzamine. Dexamisole, more than levamisole, inhibited tissular uptake of 3H-norepinephrine. Levamisole, more than dexamisole inhibited monoamine oxidase activity in vein homogenates. These interferences with release and disposition of norepinephrine may be related to antidepressant properties of tetramisole isomers.