Showing papers on "Arecoline published in 1969"

Comparison of muscarinic and nicotinic cholinergic agonists on self-stimulation behavior

Abstract: The effects of cholinergic agonists and antagonists were investigated on self-stimulation in rats with chronically implanted elcetrodes in the lateral posterior hypothalamus. Physostigmine (50-300 µg/kg s.c.) caused depression of self-stimulation. The magnitude, lateney and duration of this effect were dose-related. Arecoline (100-3000 µg/kg s.c.) had similar actions, but the depression was less dramatic and of shorter duration. Nicotine (25-600 µg/kg s.c.) caused biphasic effects; the initial depression was sometimes followed by facilitation, and the actions were much less consistent. The depressant effects of physostigmine and arecoline were blocked by scopolamine (0.5 mg/kg) and enhanced by mecamylamine (5.0 mg/kg). Methscopolamine (0.5 mg/kg) and trimethidinium (5.0 mg/kg) were much less effective. The results suggest that muscarinic cholinergic agonists which penetrate the blood-brain barrier depress self-stimulation on a central basis, whereas nicotinic cholinergic agonists have complex depressant and stimulant effects of both central and peripheral origin.

Mercapturic acid formation during the metabolism of arecoline and arecaidine in the rat

Abstract: 1 In the rat, arecoline is converted into arecaidine and both compounds are converted into N-acetyl-S-(3-carboxy-1-methylpiperid-4-yl) -l-cysteine 2 The structure of the metabolite was established by (a) synthesis, (b) conversion into N-acetyl-S-(3-methoxycarbonyl-1-methylpiperid-4-yl) -l-cysteine methyl ester, which was chromatographically identical with the synthetic material, and (c) nmr-and ir-spectral analysis of the 3-methoxycarbonyl derivative 3 In ethanolic solution, or in phosphate buffer at pH7·0, arecoline reacted with N-acetyl-l-cysteine to give N-acetyl-S-(3-methoxycarbonyl-1-methylpiperid-4-yl) -l-cysteine; under similar conditions, arecaidine reacted more slowly to give N-acetyl-S-(3-carboxy-1-methylpiperid-4-yl) -l-cysteine 4 The reaction between arecoline and glutathione or N-acetyl-l-cysteine occurred maximally at neutral pH and decreased rapidly with increasing acidity At neutral pH, the reactions were bimolecular and second-order when the reactants were in approximately equimolar concentrations and pseudo-unimolecular first-order when arecoline was in large excess 5 Consideration of the pKa values and degrees of ionization of the reactants and the effect of pH on the stoicheiometry of reaction between arecoline and glutathione or N-acetyl-l-cysteine indicated that reaction between un-ionized species occurred more readily than nucleophilic addition (AdN) reactions involving charged intermediates