Showing papers on "Arecoline published in 1975"

Betel nut constituents as inhibitors of gamma-aminobutyric acid uptake.

Abstract: THE pharmacological properties of betel nut, the dried seed of Areca catechu which is consumed in immense quantities in the East as a masticatory, are usually interpreted in terms of the cholinomimetic effects of the major alkaloid component, arecoline. Betel nut contains lesser amounts of the related alkaloid guvacoline and the amino acids arecaidine and guvacine. According to popular tradition, a mixture of crushed betel nut and lime is enveloped in leaves of Piper betle before chewing. This treatment with lime has been shown to hydrolyse almost quantitatively arecoline to arecaidine1, a well tolerated substance which lacks the typical parasympathomimetic effects of arecoline, including tremor and salivation1,2. Studies on the effects of arecaidine on the behaviour of mice indicate that this substance participates in producing some of the psychic changes ascribed to the betel mixture1,2. These betel constituents are tetrahydronicotinic acid derivatives (Fig. 1) and we have shown that nipecotic acid, ‘hexahydronicotinic acid’, is a potent inhibitor of the uptake of the central inhibitory transmitter γ-aminobutyric acid (GABA) in rat brain slices3. Nipecotic acid potentiates the depressant action of microelectrophoretically administered GABA on the firing of feline spinal neurones4. As the uptake of GABA is likely to be concerned with the inactivation of this transmitter, interference with GABA uptake could result in behavioural changes. The structural similarities between nipecotic acid and the betel nut constituents together with the above mentioned findings prompted us to examine the influence of these compounds on GABA uptake. We have found that arecaidine and guvacine are competitive inhibitors of GABA uptake in rat brain slices and we propose that some of the psychic effects of betel nut consumption may be the result of inhibition of GABA uptake.

The influence of adrenergic, dopaminergic, cholinergic and serotoninergic drugs on plasma prolactin levels in ovariectomized, estrogen-treated rats.

Abstract: Levels of plasma prolactin were estimated in ovariectomized, estrogen-treated rats following the systemic administration of several neural blocking and stimulating drugs. Phenoxybenzamine, an alpha-adrenergic blocker, at high doses, increased plasma prolactin. Phenotlamine, another alpha-adrenergic blocker, and propranolol, a beta-adrenergic blocker, also increased prolactin but the responses were small and transient. Clonidine, an alpha-adrenergic stimulating drug, elevated prolactin levels whereas the beta-adrenergic stimulator isoproterenol had no effect. Dopaminergic blockade by pimozide increased levels of prolactin while stimulation of dopamine receptors by apomorphine decreased prolactin release. Atropine (a muscarinic chilinergic blocker), arecoline (a muscarinic stimulator) and nicotine (a nicotinic cholinergic stimulating drug) did not affect basal prolactin levels. Mecamylamine (a nicotinic blocker) produced a small transient elevation in plasma prolactin. Methiothepin, an alleged serotoninergic blocker, markedly increased prolactin secretion, as did serotonin. The data suggested the involvement of several neurotransmitters in the control of basal secretion of prolactin.

Effects of arecoline and cholinesterase inhibitors on cyclic guanosine 3',5'-monophosphate and adenosine 3'.5'-monophosphate in mouse brain.

Abstract: In mice, Arecoline in vivo dose-dependently increased the cGMP concentrations of the cerebellum and the "cereberum" (= parts of cortex, hippocampus, hypothalamus, thalamus, striatum and midbrain) without influencing thecAMP levels. The cholinesterase inhibitors paraoxon and physostigmine caused an elevation only in "cerebrum", whereas the cGMP content of the cerebellum even decreased. Pretreatment with atropine prevented the rise in cGMP levels as well as the symptoms of cholinergic stimulation elicited by arecoline or paraoxon. Diazepam reduced cGMP levels below control values and blocked the effect of arecoline, while typical symptoms due to arecoline, e.g., tremor and salivation remained unaffected. The tripeptide prolyl-leucyl-glycinamide (MIF) had no effect on either cGMP values or the peripheral signs of cholinergic stimulation elicited by arecoline. The results show that elevation of cGMP in the central nervous system caused by cholinomimetic agents can be prevented not only by cholinolytics, blocking muscarinic receptors but also by influencing other mechanisms to be discussed.

Nicotine induced tremor and antidiuresis and brain nicotine levels in the rat.

Abstract: Injection of rats with 14C-labelled nicotine (3 mg/kg sc) resulted in tremor measured by an electronic device during the first minutes after the injection. The animals were decapitated immediately afterwards and tissue was removed for the measurement of nicotine and cotinine. In another set of experiments nicotine (2 mg/kg sc) was injected into alcohol anaesthetized rats, their urinary excretion was measured up to 40 min, and they were decapitated as above. Pretreatment with mecamylamine prevented nicotine-induced tremor and antidiuresis. It also lowered the brain and blood nicotine levels in tremor experiments but not in antidiuresis experiments. Restoration of tremor by arecoline did not modify the mecamylamine effects on the nicotine levels. The 2 mg/kg sc nicotine dose did not produce tremor although the brain nicotine levels at 10 min exceeded those measured at 2 min after 3 mg/kg of nicotine. It is concluded that the rate of receptor occupation is important in the nicotine tremor. Both tremor and antidiuresis correlate fairly well with brain nicotine levels whereas mecamylamine-nicotine antagonism is less clearly reflected in brain nicotine levels.

Interaction between cellular metabolism and acetylcholine turnover of rat brain cortex slices in the presence of arecoline.

Abstract: Centrally acting cholinomimetic drugs like arecoline stimulate active ion transport processes in the synaptic region. Regarding the connection between cellular metabolism and active Na"-K+-transport the effect of arecoline on the cerebral metabolic status was proved. Arecoline decreased the level of high energic phosphates and glycogen (energy charge diminished from 0,57 to 0,48) and increased the glucose consumption and lactate production. Thus, the increased rate of CoA acetylation via oxidative breakdown of pyruvate seems to be prerequisite for the cholinergically stimulated ACh synthesis.

The effect of arecoline on the structure of sleep and wakefulness in hens

Abstract: In chronic experiments on hens, studies have been made on the role of cholinergic mechanisms in regulation of the cycles "awakefulness-sleep". A cholinomimetic, arecoline, was used which stimulates M-cholinoreceptive brain neurons. Arecoline was injected intramuscularly in a dose 0.2 mg/kg of body weight. It was shown that cholinergic mechanisms are involved into the formation of "awakefulness-sleep" cycles in hens. Activation of these mechanisms facilitates paradoxical stage of sleep and expecially such its components as rapid eye movements, the decrease of tonus in neck muscles and, presumably, ponto-geniculo-occipital discharge. Arecolin affects not only the structure of paradoxical sleep, but both the awakefulness and mechanisms of slow-wave sleep stage.

[Mechanism of the inhibitory effect of acetylcholine and its analogs on sarcolemma Na, K-ATPase].

Abstract: Effect of acetylcholine on Na, K-ATPase from cardiac and skeletal rabbit muscles is studied. The inhibition of the enzyme by acetylcholine was shown to depend on the Na+/K+ ratio and Mg2+ concentration in the incubation medium. The sensitivity of Na, K-ATPase to acetylcholine and its analogues decreased as follows: acetylcholine, propionylcholine butyrylcholine, arecoline, carbacholine, choline. Muscle denervation resulted in 20-fold increase of the enzyme sensitivity to acetylcholine. Preparations of Na, K-ATPase from different muscles have the increasing sensitivity to acetylcholine in the following order: white, mixed, cardiac, denervated muscles.

Correlation between drug induced changes of acetylcholine release and acetylcholine fractions in rat brain.

Abstract: After administration of eserine, a new acetylcholine (ACh) subfraction called f+ is formed in rat brain tissue. References and methods are given for the calculation of this subfraction, which can be isolated and determined only together with the so-called "free" ACh fraction. Alterations of the f+-ACh subfraction caused by barbital, urethane, pentetrazol, arecoline and scopolamine in telencephalon, cortex and striatum of rat brain are connected with changes of ACh concentrations determined in comparable releasing tests.