Showing papers on "Arecoline published in 1984"

Binding of the nicotinic cholinergic antagonist, dihydro-beta- erythroidine, to rat brain tissue

Abstract: The nicotinic cholinergic antagonist, dihydro-beta-erythroidine, binds to two sites in rat cortical membranes with dissociation constants of 4 and 22 nM and respective apparent Bmax values of 52 and 164 fmol/mg of protein. Binding to the higher affinity site, defined by the use of 2 nM [3H]dihydro-beta-erythroidine, was saturable, reversible, and susceptible to protein denaturation. Binding was highest in the thalamus and lowest in the spinal cord and showed preferential enrichment in a synaptosomal subfraction of rat brain. Nicotine displaced [3H]dihydro-beta-erythroidine in a stereospecific manner, the (-)-isomer being approximately 6 times more potent than the (+)-isomer. The alkaloid nicotinic agonists, cytisine and lobeline, were potent inhibitors of binding, while acetylcholine in the presence of the cholinesterase inhibitor di-isopropylfluorophosphate was equipotent with (+)-nicotine. Binding was also inhibited by the muscarinic ligands, arecoline, atropine, and oxotremorine. The nicotinic antagonists mecamylamine, hexamethonium, and pempidine were essentially inactive in displacing [3H]dihydro-beta-erythroidine. These findings indicate that dihydro-beta-erythroidine binds to a nicotinic recognition site in rat brain which is neuromuscular, rather than ganglionic, in nature and that such binding is similar in several respects to that seen with nicotinic agonists. Whether such binding is to a nicotinic, as opposed to nicotinic cholinergic, recognition site or to a "common" nicotinic/muscarinic site is an issue that requires further study.

Mutagenicity of betel quid and its ingredients using mammalian test systems.

Abstract: The mutagenic potential of betel quid and its ingredients (known colloquially as PAN) were tested in two short term mutagenicity assays, the micronucleus test and a mammalian gene mutation test. Betel quid with tobacco, tobacco, betel nut and one of its alkaloids arecoline were positive in both tests. Extracts of betel quid and arecaidine (a metabolite of arecoline present in Betel nut) were negative. The data presented correlate well with our previous tumorigenicity data on these compounds.

A study of betel quid carcinogenesis. 3. 3-(Methylnitrosamino)-propionitrile, a powerful carcinogen in F344 rats

Abstract: 3-(Methylnitrosamino)propionitrile (MNPN) is formed in vitro under mild nitrosation conditions from the major areca alkaloid arecoline. It appears likely that MNPN is generated during betel quid chewing especially when tobacco is added to the quid. Upon subcutaneous injection of 1.1 mmol of MNPN in 60 subdoses, all of the 15 male and of the 15 female F344 rats developed tumors within 24 weeks. Twenty-six of the rats had tumors in two different organs at least. Twenty-seven rats had esophageal tumors, 21 nasal tumors, 11 had tongue tumors and two animals had either pharyngeal carcinomas or papillomas of the forestomach. No tumors were observed in the solvent control group. These data indicate that MNPN is a potent carcinogen.

Arecoline tumorigenicity in swiss strain mice on normal and vitamin B deficient diet

Abstract: Arecoline, a major alkaloid present in betel nut, was administered daily by gavage feeding to Swiss male and female mice at a dose of 1 mg/day/mouse five times a week, either alone or in combination with KNO3 or KNO3 + lime. Swiss mice of both sexes kept on a vitamin B complex-deficient diet were tested in a similar manner and compared with those receiving a normal diet. In the mice receiving a normal diet it was observed that arecoline induced tumors in 40% of males but failed to produce tumors in any of the females. Arecoline tumorigenicity in females was evident only when they received a vitamin B-deficient diet. Arecoline tumorigenicity was not evident in males when they were treated simultaneously with KNO3 + lime and kept on a normal diet. However, the same treatment administered to male mice kept on a vitamin B complex-deficient diet induced tumors in 39%.

A study of betel quid carcinogenesis. II. Formation of N-nitrosamines during betel quid chewing.

Abstract: In model studies, nitrosation of the major areca alkaloid, arecoline, leads to the formation of N-nitrosoguvacoline, 3-(methylnitrosamino)propionitrile (MNPN), 3-(methylnitrosamino)propionaldehyde and two unknown N-nitrosamines MNPN is a strong carcinogen in Fischer 344 rats After subcutaneous injection of 11 mmol MNPN in 60 doses, all 15 male and 15 female rats developed tumours within 24 weeks; multiple tumours occurred in 26 of the rats Eighty-seven percent of the animals had tumours of the oesophagus, 70% had nasal cavity tumours, 37% had tumours of the tongue, 7% tumours of the pharynx and 7% tumors of the forestomach At the dose used, male and female rats showed no significant difference in tumour incidence or site of tumours The formation of MNPN during betel quid chewing, although likely, has not yet been proven, while the areca-derived N-nitrosamine, N-nitrosoguvacoline (NG), has been found in the saliva of betel quid chewers at levels of 22-348 micrograms/L N-Nitrosoguvacoline levels were higher in the saliva of chewers who used betel quid together with tobacco The saliva of these chewers also contained tobacco-specific N-nitrosamines

Syntheses of an antipsychotic pyrrolo[2,3-g]isoquinoline from areca alkaloids

Abstract: Synthese des composes du titre et en particulier de la piquindone a partir d'arecoline ou d'arecolone