Showing papers on "Arecoline published in 1992"
TL;DR: In the UK, the rate of hospital admission for acute asthma is higher among Asians than among other groups in the population; betel-nut chewing may be one of several factors that affect asthma control and severity of attacks.
72 citations
TL;DR: The chromosome damage was found to be more severe on treating the cells with low concentrations and for longer duration, which mimic the effects of chronic areca nut consumption.
Abstract: The genotoxic potential of the aqueous extract of areca nut as well as arecoline, the major alkaloid of the areca nut, was tested with the help of cytogenetic markers such as sister-chromatid exchanges and chromosome aberrations, utilizing Chinese hamster ovary (CHO) cells. The continuous-treatment and pulse-treatment schedules yielded dose-dependent elevations in the frequencies of sister-chromatid exchange and chromosomal aberration in CHO cells, indicating a genotoxic effect of both the extract and arecoline. The results also imply that, besides arecoline, there may be some other water-extractable substances in the areca nut that make the extract more genotoxic. The chromosome damage was found to be more severe on treating the cells with low concentrations and for longer duration, which mimic the effects of chronic areca nut consumption.
62 citations
TL;DR: Results indicate that the aqueous and acetic acid extracts of betel nut induce relatively more unscheduled DNA synthesis than the hydrochloric acid and ethanol extracts and arecoline.
Abstract: Aqueous, acetic acid, hydrochloric acid and ethanol extracts of betel nut (Areca catechu L.) have been found to induce unscheduled DNA synthesis in Hep 2 cells obtained from human larynx carcinoma, in vitro. Different concentrations of extracts of betel nut induced dose-dependent unscheduled DNA synthesis in Hep 2 cells. Together with the viability of the Hep 2 cells, our results indicate that the aqueous and acetic acid extracts of betel nut induce relatively more unscheduled DNA synthesis than the hydrochloric acid and ethanol extracts and arecoline. The carcinogenic potency of raw and unprocessed betel nut of North-East India used in this study is discussed.
34 citations
TL;DR: Results from in vivo experiments in mice and rats showed that these new substances, 1-[4-chlorophenyl] oxycarbonyl-1,2,5,6-tetrahydropyridine-3- carboxaldehyde-O-methyloxime ( 16 = RU 47213) in particular, have cholinomimetic properties that compare favourably with those of the parent compounds.
14 citations
TL;DR: In this study, muscarinic agonism for arecoline series is governed by strict structure-activity relationships, as previously observed for other agonist series.
13 citations
TL;DR: Several reportedly selective and non-selective muscarinic agonists were examined for comparative pharmacological potency in three diverse models: the guinea pig ileum, the pithed rat, and the mouse charcoal meal transit test.
Abstract: 1. Several reportedly selective (McN-A-343, M1; RS-86, M2; pilocarpine, M3) and non-selective (oxotremorine, acetylcholine, cis-dioxalone, arecoline, muscarine) muscarinic agonists were examined for comparative pharmacological potency in three diverse models: the guinea pig ileum, the pithed rat, and the mouse charcoal meal transit test. 2. In the guinea pig ileum, all of the compounds examined were associated with concentration-dependent contractions. 3. The apparent order of potency in the isolated ileum was cis-dioxalone greater than acetylcholine greater than oxotremorine greater than arecoline greater than RS-86 greater than pilocarpine greater than McN-A-343. 4. The pA2 values for atropine and pirenzepine in the ileum ranged from 8.4 to 9.4 and 6.1 to 7.7, respectively, indicative of a single receptor, most likely M3. 5. In the mouse charcoal meal transit test, non-selective muscarinic agonists produced dose-dependent increases in gastrointestinal transit, while selective agonists failed to produce any significant changes. 6. Scopolamine methylbromide, a peripherally acting non-selective muscarinic antagonist, significantly reduced the ability of muscarine to increase transit. 7. The compounds were further examined for dose-dependent pressor effects in the pithed rat, which are known to be mediated by stimulation of M1-receptors in sympathetic ganglia. 8. McN-A-343 produced the greatest pressor response, as measured by the percent increase in mean pressure, followed by pilocarpine. 9. Pirenzepine antagonized the pressor response of McN-A-343 and pilocarpine in a dose-dependent manner.
10 citations
TL;DR: It is concluded that muscarinic receptor density in MDCK cells is 50 times higher than that in inner medullary collecting duct cells, and this intracellular messenger system may be partially responsible for the action of cholinergic agonists in these cells and in the kidney.
Abstract: Muscarinic-type cholinergic receptors coupled to the phosphoinositide (PI) second messenger system are reported to be present in the inner medullary collecting duct cells. Madin-Darby canine kidney (MDCK) cells have several characteristics of collecting duct cells and have been shown to respond to muscarinic agonists. To determine if MDCK cells have PI-coupled muscarinic receptors, the radioligand binding and the effects of cholinergic agonists and antagonists on PI hydrolysis in MDCK cells were studied. The specific binding of [3H]1-quinuclidinyl benzilate ([3H]QNB), a muscarinic antagonist, to MDCK cell membranes had a Kd = 88 +/- 7 pM and a Bmax = 1464 +/- 88 fmol/mg of protein. The displacement of [3H]QNB from MDCK cell membranes by various cholinergic antagonists and agonists showed the order of potency: atropine greater than 4-diphenylacetoxy N-methylpiperidine (4-DAMP) greater than p-fluorohexahydrosiladifenidol greater than pirenzepine greater than metoctramine greater than arecoline greater than carbachol. The cholinergic agonists carbachol and arecoline stimulated PI hydrolysis in a concentration-dependent manner with an EC50 of 3.7 and 1.3 microM, respectively. Muscarinic antagonists abolished carbachol-stimulated PI hydrolysis in the following order of potency: atropine greater than 4-DAMP greater than pirenzepine much greater than methoctramine. The order of potency of muscarinic antagonists is consistent with the characteristics of the M3 subtype of muscarinic receptors. It is concluded that: (1) muscarinic receptor density in MDCK cells is 50 times higher than that in inner medullary collecting duct cells; (2) muscarinic receptors in MDCK cells are putative M3 subtype; and (3) muscarinic receptors in MDCK cells are functionally coupled to the PI second messenger system. This intracellular messenger system may, at least, be partially responsible for the action of cholinergic agonists in these cells and in the kidney.
10 citations
TL;DR: In this paper, the enantiomorphic conformations of arecoline have been evaluated as muscarinic agonists, and their enantiomers 8b and 2b have been prepared as rigid analogues of the enantionomous conformations.
8 citations
TL;DR: The differential HVA response to a muscarinic agonist in Alzheimer's disease is suggestive of an alteration inMuscarinic receptor response, which may have potential implications for the pathophysiology and treatment of Alzheimer's Disease.
Abstract: The effects of the muscarinic agonist, arecoline, on the concentration of homovanillic acid (HVA) in the cerebrospinal fluid of patients with Alzheimer's disease (AD) and controls were examined. Patients and controls received intravenous infusions of arecoline and a lumbar puncture was performed four hours after the infusion began. Arecoline induced a significant increase in the concentration of HVA in cerebrospinal fluid of Alzheimer's disease patients (p<.01) but not in controls. The differential HVA response to a muscarinic agonist in Alzheimer's disease is suggestive of an alteration in muscarinic receptor response. This finding may have potential implications for the pathophysiology and treatment of Alzheimer's disease.
8 citations
TL;DR: The data suggest that the ability to form H-bonds is an important factor for the ability of 1 to stimulate M1 muscarinic receptors in the CNS.
6 citations
TL;DR: In this article, a series of 1-alkyl-1,2,5,6-tetrahydropyridine-3-carboxaldehyde- O -alkyloximes was synthesized and biologically evaluated in a battery of in vitro and in vivo assays.
Abstract: On the basis of the knowledge acquired from basic studies of several known arecoline derivatives about the structural requirements for potent agonistic activity and oral efficacy, a series of 1-alkyl-1,2,5,6-tetrahydropyridine-3-carboxaldehyde- O -alkyl-oximes was synthesized and biologically evaluated in a battery of in vitro and in vivo assays. The most interesting molecules to emerge from the primary screening, 1,2,5,6-tetrahydropyridine-3-carboxaldehyde- O -methyloxime hydrochloride ( 11 , RU 35963), 1-methyl-1,2,5,6-tetrahydropyridine-3-carboxaldehyde- O -methyloxime hydrochloride ( 12 , RU 35926), and 1,2,5,6-tetrahydropyridine-3-carboxaldehyde- O -propargyloxime hydrochloride ( 30 , RU 47029) and 1-methyl-1,2,5,6-tetrahydropyridine-3-carboxaldehyde- O -propargyloxime hydrochloride ( 33 , RU 35986), were evaluated more extensively, and their cholinomimetic profile was compared with that of the parent molecule, arecoline. The pharmacological results after oral administration to mice and rats revealed that their efficacy is 2–3 orders of magnitude higher than that of arecoline, and, in addition, they show a longer duration of action. The 4 aldoximes showed anti-amnesic properties in many respects superior to those of arecoline. Their anti-amnesic doses were 2 orders of magnitude lower than those inducing obvious cholinergic symptoms, and 3–5 orders of magnitude lower than the lethal doses. These new compounds can be regarded as potential candidates for clinical studies in AD (Alzheimer's disease) patients.
TL;DR: The mechanistic hypothesis that upon absorption into skin, arecoline induces a local inflammatory response and a systemic ACD response is supported, as characterized by classical immunological tests employing inbred mice.