Benzoyltropine and tropacocaine are two contaminants of street-cocaine reported to have parasympatholytic activity. Because the mechanism underlying this activity is obscure, we investigated the effects of these compounds on several cholinergic processes: sodium-dependent choline uptake, sodium-independent choline uptake, acetylcholine synthesis, acetylcholine release (spontaneous and veratridine-induced) and binding of [3H]quinuclidinyl benzylate to muscarinic receptors. These studies used rat cerebral cortical synaptosomes, except for the receptor-binding studies, which used whole brain plasma membranes. Benzoyltropine and tropacocaine each inhibited sodium-dependent choline uptake and acetylcholine synthesis in a dose-related manner that was competitive with extracellular choline. Benzoyltropine was 4 to 5 times more potent in both actions than tropacocaine. Sodium-independent choline uptake was not affected by either compound. Benzoyltropine (30 microM) had no effect on the sodium-dependent uptake of norepinephrine, gamma-amino-butyric acid, glutamate or serotonin; tropacocaine (30 microM) inhibited only norepinephrine uptake at this concentration. Benzoyltropine and tropacocaine each inhibited the spontaneous and veratridine-induced release of newly synthesized acetylcholine, but not via activation of presynaptic muscarinic receptors. Instead, each compound was able to attenuate the oxotremorine-induced inhibition of the release of acetylcholine, suggesting antimuscarinic activity. Binding experiments showed that benzoyltropine and tropacocaine were, respectively, about 1,000- and 10,000-fold less potent than scopolamine as receptor antagonists. Finally, we demonstrated that benzoyltropine accumulates in the rat brain after its peripheral injection (10 mg/kg i.p.) and remains there with a half-life similar to that of cocaine.(ABSTRACT TRUNCATED AT 250 WORDS)
        
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Meyer EM, Potter LT, De Vane CL, Irwin I, MacKay SL, Miller R, Ruttenber AJ (1990) Effects of benzoyltropine and tropacocaine on several cholinergic processes in the rat brain Journal of Pharmacology & Experimental Therapeutics254: 584-90
Meyer EM, Potter LT, De Vane CL, Irwin I, MacKay SL, Miller R, Ruttenber AJ (1990) Journal of Pharmacology & Experimental Therapeutics254: 584-90