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Journal of Pharmacology and Experimental Therapeutics

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Abstract

Effects of benzoyltropine and tropacocaine on several cholinergic processes in the rat brain.

E M Meyer, L T Potter, C L De Vane, I Irwin, S L MacKay, R Miller and A J Ruttenber
Journal of Pharmacology and Experimental Therapeutics August 1990, 254 (2) 584-590;
E M Meyer
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L T Potter
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C L De Vane
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I Irwin
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S L MacKay
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R Miller
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A J Ruttenber
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Abstract

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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Journal of Pharmacology and Experimental Therapeutics
Vol. 254, Issue 2
1 Aug 1990
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Abstract

Effects of benzoyltropine and tropacocaine on several cholinergic processes in the rat brain.

E M Meyer, L T Potter, C L De Vane, I Irwin, S L MacKay, R Miller and A J Ruttenber
Journal of Pharmacology and Experimental Therapeutics August 1, 1990, 254 (2) 584-590;

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Abstract

Effects of benzoyltropine and tropacocaine on several cholinergic processes in the rat brain.

E M Meyer, L T Potter, C L De Vane, I Irwin, S L MacKay, R Miller and A J Ruttenber
Journal of Pharmacology and Experimental Therapeutics August 1, 1990, 254 (2) 584-590;
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