Showing papers on "Arecoline published in 1996"
TL;DR: Because of repeated and long-term exposure to arecoline, BQ chewers could be more susceptible to periodontal damage and less responsive to new attachment procedures.
Abstract: Because betel quid (BQ) chewing has been linked to a higher prevalence of periodontal diseases, the pathobiological effects of arecoline, a main alkaloid found in areca nut, were investigated in cultured human gingival fibroblasts. At concentrations higher than 0.4 mM, arecoline inhibits cell attachment, cell spreading and cell migration in a dose-dependent manner. These inhibitory effects were associated with intracellular depletion of glutathione (GSH). At concentrations of 0.4 mM and 1 mM, arecoline depleted about 26% and 45% of GSH after 2 h incubation. Exposure of cells to arecoline at concentrations lower than 0.4 mM for 2 h showed no significant decrease in either cell viability or intracellular GSH. However, incubation of cells for 24 h in 1 mM are colined decreased the cell numbers to only 35% of those in the untreated control. Arecoline also decreased cell growth and collagen synthesis in a dose-dependent manner. Because of repeated and long-term exposure to arecoline, BQ chewers could be more susceptible to periodontal damage and less responsive to new attachment procedures.
74 citations
TL;DR: To study the pharmacokinetics and pharmacodynamics of intravenously administered arecoline in subjects with Alzheimer's disease.
Abstract: Objective
To study the pharmacokinetics and pharmacodynamics of intravenously administered arecoline in subjects with Alzheimer's disease.
Methods
Plasma arecoline concentrations were measured during and after high-dose (i.e., 5 mg intravenously over 30 minutes) and up to 2 weeks of continuous multiple-dose steady-state intravenous infusions of arecoline in 15 subjects with mild to moderate Alzheimer's disease. During multiple-dose infusions, the dose of arecoline was escalated from 0.5 to 40 mg/day. Psychometric tests were administered at baseline and every other dose to determine an “optimal dose” for each subject. This dose then was administered for 1 week using a randomized, placebo-controlled, double-blind, crossover design. Plasma drug concentrations were measured by GC-MS.
Results
The optimal dose of arecoline varied fourfold across subjects (4 mg/day, n = 6; 16 mg/day, n = 3) with mean plasma half-lives of 0.95 ± 0.54 and 9.3 ± 4.5 (SD) minutes. Clearance and volume of distribution were 13.6 ± 5.8 L/min and 205 ± 170 (SD) L, respectively. At the dose that optimized memory, the mean plasma level was 0.31 ± 0.14 (SD) ng/ml, and it predicted the optimal dose in all subjects.
Conclusions
Because optimal dose variation is due to differing plasma kinetics, the plasma arecoline level measured at a single infusion rate can be used to choose the optimal dose for memory enhancement in patients with Alzheimer's disease.
Clinical Pharmacology & Therapeutics (1996) 60, 276–282; doi:
58 citations
TL;DR: Results are consistent with previous studies which demonstrated that another selective 5-HT3 receptor antagonist, WAY-100289, significantly reversed the cognitive deficits in water maze performance induced by ibotenic acid lesions of forebrain cholinergic projection system.
Abstract: The effects of the 5-HT3 receptor antagonists, WAY-100579 and ondansetron (both at doses of 0.001, 0.01 and 0.1 mg/kg SC) and the muscarinic receptor agonist arecoline (1.0 mg/kg SC), on spatial learning and memory in the water maze were examined in rats after combined S-AMPA lesions to the nucleus basalis and medial septal brain regions. Lesioned rats showed substantially increased latency to find the submerged platform, and spent less time searching in the correct quadrant, and more time circling the periphery of the pool, relative to controls. Lesioned rats treated with WAY-100579, ondansetron and arecoline exhibited marked improvement in these parameters of learning relative to lesioned animals, with arecoline-treated animals showing the most substantial recovery. Linear dose-related trends of improvement were seen with both of the 5-HT3 antagonists. In probe trials, testing retention of the platform position 24 and 72 h after the end of training, control rats exhibited substantial superiority relative to lesioned rats in accuracy of search in the training quadrant and former platform area, matched by rats treated with arecoline on the first, and by rats treated with the two higher doses of WAY-100579 and ondansetron on the second probe trial. These results are consistent with our previous studies which demonstrated that another selective 5-HT3 receptor antagonist, WAY-100289, significantly reversed the cognitive deficits in water maze performance induced by ibotenic acid lesions of forebrain cholinergic projection system. Therefore, selective 5-HT3 receptor antagonists may provide a novel effective therapy for treating cognitive deficits associated with degeneration of central cholinergic neurones, such as Alzheimer's disease or age-associated memory impairment.
48 citations
TL;DR: It is demonstrated that young rats fail to remember the passive-avoidance response but that retention for this task can be specifically enhanced with cholinomimetic drugs.
45 citations
Journal Article•
TL;DR: In this article, the authors investigated the effect of tannic acid and catechin on the growth of salivary and selected oral microorganisms of areca nut, aqueous extracts of the nut, its major alkaloid arecoline and the components of its tannin fraction.
42 citations
TL;DR: N-Nitrosoguvacoline (NG) is the only one N-nitrosamine found in Taiwanese betel quid chewing saliva and mutagenic studies showed that crude alkaloid extracts of areca fruit and arecoline were active in Salmonella typhimurium TA100, and NG was weakly active in TA98 and TA100.
Abstract: In Taiwan, betel quid is a natural masticatory, which is composed of fresh green areca fruit, Piper betle and slaked lime paste. Areca fruit contains some alkaloids, of which arecoline is the major one. N-Nitrosoguvacoline (NG), one of the N-nitrosation products of arecoline, is the only one N-nitrosamine found in Taiwanese betel quid chewing saliva. The mutagenic studies in Ames Salmonella microsome test showed that crude alkaloid extracts of areca fruit and arecoline were active in Salmonella typhimurium TA100, and NG was weakly active in TA98 and TA100. The activities in both arecoline and NG decreased further in the presence of rat liver S9 mix. Nitrite was significantly consumed during the N-nitrosation of arecoline and sodium nitrite at acidic condition (pH 3), whereas the formation of NG was favored at neutral condition (pH 7). Crude phenolic extracts of leaf and inflorescence of Piper betle inhibited the formation of NG by blocking the nitrite. However, a high amount of crude phenolic extracts of areca fruit enhanced the formation of NG.
40 citations
TL;DR: Results indicated there were significant differences among tests in the dose at which most patients showed improved cognitive performance, and these differences may have therapeutic significance, as verbal ability tended to improve at low doses of arecoline, whereas attention and visuospatial ability tendedTo improve at higher doses ofArecoline.
36 citations
TL;DR: It appears that the cholinergic receptor on the schistosome muscle fibres may be of the nicotinic type, but that its pharmacology is different from that of Nicotinic receptors of vertebrates as well as of nematodes or a variety of other invertebrates.
Abstract: Cholinergic compounds inhibit FMRFamide-induced contractions in dispersed muscle fibres isolated from adult Schistosoma mansoni. Acetylcholine (ACh) was the most effective cholinergic agonist tested with an EC 50 < 100 no. Less effective were propionylcholine and arecoline with EC 50 < 1 μM and butyrylcholine and carbachol with EC 50 < 10 μM. Choline, muscarine, pilocarpine, nicotine, DMPP (1,1-dimethylphenylpiperazine ) and levamisole were all ineffective. Amongst tested antagonists, d-tubocurarine (100 μM), mecamylamine (1 mM), atropine (1 mM), scopolamine (1 mM) and quinuclidinyl benzilate (10 μM) were all ineffective. Bicuculline, picrotoxin and strychnine were also ineffective. However α-bungarotoxin, at 100 nM, was able to block the inhibitory ACh effect. From these data it appears that the cholinergic receptor on the schistosome muscle fibres may be of the nicotinic type, but that its pharmacology is different from that of nicotinic receptors of vertebrates as well as of nematodes or a variety of other invertebrates.
28 citations
TL;DR: The find implies that the adjuvant ingredients, catechu and liquorice root extract provide not only a flavor but also an antagonist against the genotoxicity of arecoline and fluoride containing betel quid.
Abstract: The purpose of this study is to explore the mutual interactions among the chemical ingredients of betel quid including arecoline, sodium fluoride, catechin and glycyrrhizin in producing genotoxicity on Chinese hamster ovary (CHO) cells using the micronucleus method. Our results show that arecoline at a rather low concentration of 0.2–2 μ M which could be in the oral cavity during betel quid chewing and NaF (0.8–2.4 mM) significantly elevated the number of micronucleated cells in a concentration-dependent manner. In addition, significant prolongation of cell cycles was observed by treatment with arecoline (≥2.0 μ M) or NaF (2.4 mM) in CHO cells. Both catechin and glycyrrhizin could antagonize not only the increased micronucleated cells induced by arecoline and NaF but also the prolonged cell cycle induced by arecoline in CHO cells. This finding implies that the adjuvant ingredients, catechu and liquorice root extract provide not only a flavor but also an antagonist against the genotoxicity of arecoline and fluoride containing betel quid.
17 citations
TL;DR: Modulation in competing potential pathways of biotransformation system enzymes in lactating dams may affect the rate and extent of maternal detoxication and thus influence the passage of metabolites of administered xenobiotics to the suckling neonate.
Abstract: The present study assesses the potential of arecoline alkaloid to translactationally modify the chemopreventive efficacy of curcumin (diferuloyl methane) via neonatal modulation of hepatic biotransformation system enzymes. Curcumin (0.4 g/kg body wt/day) induced a significant increase in the hepatic levels of glutathione‐S‐transferase (GST), acid‐soluble sulfhydryl (SH), cytochrome b5, and cytochrome P‐450 in lactating dams and F1 pups at 14 or 21 days. Arecoline (20 mg/kg body wt/day) could not modulate the hepatic GST and SH levels, although significant induction was observed in the levels of cytochrome b5 and cytochrome P‐450 in dams and suckling pups. Significant enhancement of hepatic GST, SH, cytochrome b5, and cytochrome P‐450 levels was observed in groups treated with curcumin + arecoline. Curcumin‐induced levels of GST and SH were depressed whereas cytochrome b5 and cytochrome P‐450 were further elevated by curcumin + arecoline treatment. The elevated levels of Phase I enzymes were more ...
15 citations
TL;DR: It is concluded that the sensitivity of brain muscarinic receptor to its agonists is increased in acute nicotine tolerant rats, mice and rabbits.
TL;DR: These studies tested the effect of arecoline, a nonselective muscarinic agonist, administered either acutely or by chronic peripheral infusion via osmotic minipumps, on a scopolamine-induced deficit in a Stone (14 unit) T-maze task in rats, and indicate that dose selection is of great importance when employing are coline in tests of learning and memory.
Abstract: These studies tested the effect of arecoline, a nonselective muscarinic agonist, administered either acutely or by chronic peripheral infusion via osmotic minipumps, on a scopolamine-induced deficit in a Stone (14 unit) T-maze task in rats. Scopolamine alone (0.125-1.0 mg/kg, IP) dose-dependently impaired maze acquisition, increasing maze run-times and to a lesser extent, the number of errors committed. Neither acute administration of arecoline (5.0 and 10.0 mg/kg, IP), when tested against a deficit induced by scopolamine (0.25 mg/kg, IP), nor chronic arecoline administration (30 and 50 mg/kg per 24 h), when tested against a deficit induced by scopolamine (0.5 mg/kg), were able to ameliorate the decrements in maze performance. In fact, the higher dose of arecoline (50 mg/kg per 24 h) infused over 10 days potentiated the scopolamine-induced deficit, with respect to latency. These data indicate that dose selection is of great importance when employing arecoline in tests of learning and memory and that the influence of the method of administration of arecoline on the behavioural outcome warrants further study.
TL;DR: In lactating dams the modulated levels of hepatic biotransformation system enzymes potentially could affect the detoxication efficacy of administered chemicals besides influencing the rate and extent of passage of metabolites to suckling neonate.
Abstract: The present study evaluates the potential of arecoline alkaloid on chlorophyllin (CHL) modulated levels of hepatic biotransformation system enzymes in suckling neonate and lactating mice. CHL [50, 100, or 200 mg/kg body weight (b.w.)/day] induced significant increases in the hepatic levels of glutathione S-transferase (GST) and sulfhydryl (-SH) in lactating dams and suckling pups of 14 or 21 days. The depleted level of hepatic Cytochrome (Cyt.) P-450 was observed only in lactating dams given 200 mg/kg b.w. CHL. Arecoline (20 mg/kg b.w.) could depress the CHL-induced levels of hepatic GST and -SH, while Cyt. P-450 and Cyt. b5 levels remained unaltered by arecoline alone or arecoline plus CHL treatment. In lactating dams the modulated levels of hepatic biotransformation system enzymes potentially could affect the detoxication efficacy of administered chemicals besides influencing the rate and extent of passage of metabolites to suckling neonate.
TL;DR: The observations suggest that although both the modulation of body temperature and NK cell activities are integrated at the level of the hypothalamus, these pathways of regulation can be differentiated.
Abstract: Arecoline, a muscarinic cholinergic agonist, was found to depress body temperature and elevate the activity of preactivated natural killer (NK) cells. To demonstrate that the unconditioned responses produced by arecoline were mediated through central nervous system pathways, we used the drug as an unconditioned stimulus. By pairing camphor odor (conditioned stimulus) with arecoline (unconditioned stimulus), it was possible to simultaneously condition both a decrease in body temperature and augmentation of NK cell activity. The observations suggest that although both the modulation of body temperature and NK cell activities are integrated at the level of the hypothalamus, these pathways of regulation can be differentiated.