EFFECT OF COCAINE, DENERVATION AND DECENTRALIZATION ON THE RESPONSE OF THE NICTITATING MEMBRANE TO VARIOUS SYMPATHOMIMETIC AMINES

¹ Department of Pharmacology, Harvard Medical School, Boston, Massachusetts

Dose-response curves of 14 sympathomimetic amines were studied on the nictitating membrane of spinal cats. Some of these amines had only direct effects (e.g., norepinephrine), some had only indirect effects (e.g., tyramine), while others had both direct and indirect actions (e.g., ephedrine).

Cocaine antagonized all indirect effects of tyramine- and of ephedrine-like amines. The well-known sensitizing effect of cocaine was found to be very pronounced with all compounds which, as a characteristic structural feature, possessed a phenolic hydroxyl group in the meta-position; the para-OH analogues and the corresponding parent compounds with no phenolic hydroxyl groups were much less or not at all potentiated by cocaine, even when these amines had direct actions. Hence the sensitizing action of cocaine is more specific than hitherto assumed.

Decentralization, on the other hand, caused supersensitivity to all amines with direct, mixed or indirect actions; this supersensitivity, which was studied with nine amines, was of about equal magnitude for all.

The effect of denervation was very similar to that of cocaine, but certain differences were also observed. It is proposed that the effect of denervation is best described as corresponding to the sum of the effects of cocaine, of decentralization and of depletion of the norepinephrine stores.