STERIC ASPECTS OF ADRENERGIC DRUGS. XII. SOME PERIPHERAL EFFECTS OF (±)-ERYTHRO-AND (±)-THREO-METHYLPHENIDATE

¹ College of Pharmacy, The Ohio State University, Columbus, Ohio

The ability of the diastereoisomers of methylphenidate to enhance responses to norepinephrine correlates with their known abilities to produce central nervous system stimulation. On the basis of a shift of the dose-response curve in a horizontal manner to the left, threo-methylphenidate (2 mg/kg) enhanced norepinephrineinduced responses of the cat nictitating membrane about 30-fold. In a like manner, erythro-methylphenidate (20 mg/kg) produced about a 5-fold shift of the norepinephrine dose-response curve. In potentiating norepinephrine-induced contractions of the rat vas deferens, molar concentrations of the isomers causing equal effects showed a 300-fold difference, with the threo-isomer requiring the lesser concentration. In concentrations up to 3 x 10^-4 M, the erythro-isomer was not able to reduce tyramine-induced responses on the isolated rat vas deferens preparation, whereas the threo-isomer (10^-4 M) substantially reduced these responses. Neither isomer (10^-3 M) was able to protect the effects of norepinephrine from block by Dibenamine (10^-6 M, 10-min incubation). There was a tendency for the threo-isomer to inhibit the neuronal accumulation of norepinephrine by rat isolated vasa deferentia, whereas this tendency was absent with the erythro-isomer. In histochemical studies the threo-isomer completely prevented restoration of fluorescence by Cobefrin in the catecholamine-depleted rat iris, whereas the erythro-isomer failed to prevent it.