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Results for “MECAMYLAMINE”

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PubMed1985

Mecamylamine pretreatment counteracts cigarette smoke induced changes in hypothalamic catecholamine neuron systems and in anterior pituitary function.

We have studied the effects of acute, intermittent exposure to tobacco smoke on discrete hypothalamic CA nerve terminal networks and on neuroendocrine function by means of quantitative histofluorimetrical determinations of catecholamine (CA) fluorescence in sections of rat brain and by radioimmunoassay procedures for hormones. Acute intermittent exposure to cigarette smoke induced a lowering of NA levels and increased NA turnover in discrete hypothalamic nerve terminal regions. This exposure also induced increases in DA turnover in the median eminence. The cigarette smoke lowered TSH, prolactin, LH and FSH serum levels, but induced an increase in serum corticosterone concentrations. To determine if the above mentioned changes in neuroendocrine function were nicotine mediated, a cholinergic nicotine-like blocking agent, mecamylamine, was administered prior to exposure to cigarette smoke. Pretreatment with mecamylamine (1.0 mg kg-1) counteracted the cigarette smoke induced changes in CA levels and turnover in all hypothalamic CA nerve terminal regions as well as the changes in serum levels of the pituitary hormones and corticosterone. It is suggested that acute intermittent exposure to cigarette smoke, via its nicotine component, lowers TSH, prolactin, LH and FSH secretion at least in part through activation of the tubero-infundibular DA neurons. Furthermore, the nicotine component of the cigarette smoke is suggested to induce the increase in corticosterone serum levels via increasing NA turnover in the paraventricular hypothalamic nucleus.

Animals↗

PubMedDate not supplied

Effect of diisopropylfluorophosphate and atropine or mecamylamine on acetylcholine levels in the central nervous system of the rat.

The effect on acetylcholine levels caused by diisopropylfluorophosphate, either alone or in combination with atropine or mecamylamine, has been studied in the olfactory brain, medulla pons and cortex of the rat. At sublethal doses (0.25 and 0.5 mg/kg), diisopropylfluorophosphate reduced the acetylcholine levels. This effect was completely antagonized by atropine in the medulla pons and by mecamylamine in the medulla pons, olfactory brain and partly in the cortex. These observations suggest that the reduction of acetylcholine levels at low doses of diisopropylfluorophosphate is mediated by a muscarinic system in the medulla pons and by a nicotinic system in the medulla pons, the olfactory brain and also, in part, in the cortex.

Acetylcholine↗

PubMed1964

THE SYMPATHETIC POSTGANGLIONIC FIBRE AND THE BLOCK BY BRETYLIUM; THE BLOCK PREVENTED BY HEXAMETHONIUM AND IMITATED BY MECAMYLAMINE.

Acetylcholine, in the presence of atropine, has an action like that of sympathetic stimulation. When injected into the splenic artery it causes contraction of the spleen, but this action is blocked by hexamethonium; stimulation of the splenic nerves, however, is still effective. Thus hexamethonium distinguishes between sympathetic nerve stimulation and the action of acetylcholine. If bretylium is used instead of hexamethonium, there is no such distinction, for bretylium blocks the response to nerve stimulation as well as that to acetylcholine. It appeared that hexamethonium might block the action of acetylcholine by preventing its entry into the sympathetic fibre. Acetylcholine has some structural similarity to bretylium, since acetylcholine is a derivative of trimethylammonium and bretylium is a derivative of dimethylethylammonium. It has been found that hexamethonium, pentolinium and hemicholinium (HC-3), which are all bis-quaternary compounds, block the action of bretylium, presumably by preventing its entry into the fibre. Consistent with the view that ability to enter the fibre is important is the observation that mecamylamine and pempidine, which are ganglion-blocking agents, but not either mono- or bis-quaternary compounds, often abolish the response to stimulation of the sympathetic postganglionic fibre.

Acetylcholine↗

PubMed1963

Bacteriological and histological studies of the small intestine of rats treated with mecamylamine.

Rats were injected intraperitoneally with mecamylamine (Inversine) in doses that were believed to have reduced peristaltic activity in the small intestine. Large numbers of Escherichia coli were present throughout the lumen of the small intestine of animals treated for two or three days and killed within three hours of the last dose of the drug. Histological changes in the small intestinal mucosa of these animals included an increase in the number of goblet cells and shortening and thickening of the villi. Bacteria invaded the intestinal wall of some of the animals. Animals killed 24 hours after the last dose of the drug showed no significant change from the normal controls. The findings support the hypothesis that bacteria are removed mechanically from the normal small intestine by peristalsis. Certain of the histological changes are similar to those seen in the small intestine in malabsorptive conditions in man and the relationship between hypomotility, the bacterial population, and malabsorption is discussed.

Animals↗

PubMed1987

The role of Renshaw cells in locomotion: antagonism of their excitation from motor axon collaterals with intravenous mecamylamine.

The contribution of Renshaw cell (RC) activity to the production of fictive locomotion in the mesencephalic preparation was examined using the nicotinic antagonist mecamylamine (MEC). After the i.v. administration of 3 doses of MEC (1.0 mg/kg) the following observations were made: 1) ventral root (VR) evoked discharge of RCs was decreased by up to 87.7%, 2) recurrent inhibitory postsynaptic potentials recorded in alpha motoneurons were greatly reduced or abolished, and 3) the rhythmic firing of RCs during the fictive step cycle was abolished in 83% of the cells examined. Locomotor drive potentials (LDPs) in motoneurons persisted during the fictive step cycle after MEC administration. Bursts of motoneuron firing during each fictive step cycle were characterized by increased frequency and number of spikes after MEC, although the burst duration was unaltered for similar step cycle lengths. A greater number and frequency of spikes per burst was also observed in Ia inhibitory interneurons (IaINs), which remained rhythmically active after MEC administration. It is concluded that Renshaw cells are not an integral part of the spinal central pattern generator for locomotion, nor do they control the timing of the motoneuron or IaIN bursts of firing during fictive locomotion. The data are consistent with a role for RCs in limiting the firing rates of motoneurons and IaINs during each burst.

Animals↗

PubMed1983

Deficits in passive avoidance learning in young rats following mecamylamine injections in the hippocampo-entorhinal area.

Young rats 11, 13, 16, and 20 days old were injected bilaterally with the nicotinic antagonist mecamylamine hydrochloride (5, 50, and 100 micrograms on each side) into the posteroventral hippocampo-entorhinal (VHE) area and trained on a "cool-draft-stimulus" passive avoidance task. The data showed impaired acquisition and reduced resistance to extinction. The deficits observed were age- and dose-dependent, rats being highly sensitive to the drug when 11 and 13 days old and decreasingly responsive up to day 20. The results may indicate that nicotinic cholinergic sites in the VHE area mediate passive avoidance learning in the young rat as soon as acquisition emerges. Muscarinic cholinergic mechanisms only develop later in this region, becoming progressively more important for passive avoidance behavior.

Animals↗

PubMed1979

Effects of nicotine, mecamylamine, and hexamethonium on shock-induced fighting, pain reactivity, and locomotor behaviour in rats.

Three series of experiments were performed to evaluate possible nicotinic cholinergic influences on fighting behaviour in rats. Each series consisted of three tests (naive animals in each test); shock-induced fighting, pain threshold estimation and locomotor activity. In the first series, nicotine (0.25 -- 1.00 mg/kg) was found to produce a dose-dependent inhibition of fighting without altering shock thresholds. However, the highest dose used also significantly reduced rearing in the activity test. In the second series, mecamylamine (a centrally active antinicotinic) produced a facilitation of fighting at low doses (2.5 mg/kg) and an inhibition at higher doses (10 mg/kg). Whilst these effects were unrelated to changes in shock thresholds, the high dose resulted in a reduction in both horizontal activity and rearing. Finally, as a control for possible peripheral effects of nicotinic blockage, a third series examined the behavioural effects of hexamethonium. Low doses of this compound (2.25 -- 4.5 mg/kg) had little effect on fighting whilst higher doses (9 -- 18 mg/kg) attenuated these responses. Interestingly, although hexamethonium had no effect on shock thresholds, the highest dose (18 mg/kg) produced a facilitation of horizontal activity. Results are discussed in relation to the hypothesis of central nicotinic cholinergic inhibition of agonistic behaviour.

Aggression↗

PubMed1984

Protection against diisopropylfluorophosphate intoxication by pyridostigmine and physostigmine in combination with atropine and mecamylamine.

Atropine (A), mecamylamine (M), pyridostigmine (Py) and physostigmine (Ph) are pretreatment components of Mix I (A = 0.79, M = 0.79, Py = 0.056 mg/kg) and Mix II (A = 0.79, M = 0.79, Ph = 0.026 mg/kg). They have been successfully used in antagonizing Soman intoxication in experimental animals. Rats were pretreated with either Mix I or Mix II and subsequently exposed to diisopropylfluorphosphate (DFP). Pretreatment with Mix I or Mix II (i.m.) 30 min before DFP (i.v.) protected rats from the lethal effects of DFP. The protective ratios were 2.8 (Mix I) and 6.9 (Mix II). Changes in brain levels of acetylcholine (ACh) were measured to help understand the basis for effectiveness of these pretreatments. In the absence of DFP, pretreatments had no significant (P greater than 0.05) effect on bound or free ACh. Pretreatment did not prevent the DFP-induced rise in bound and free ACh nor the agent-induced physical incapacitation at 30 min post exposure. At 2 h after DFP exposure, rats pretreated with Mix II, but not Mix I, showed significant recovery from signs of physical incapacitation. At 30 min after the administration of 3.3 mg/kg of DFP (i.v.), the levels of free and bound ACh in rats given Mix I or Mix II pretreatment increased above control levels by 705% and 116% and 120% and 43%, respectively. By 2 h after DFP, cerebral ACh levels had changed to 437% and 91% with Mix I pretreatment and 26% and 50% with Mix II pretreatment. These data suggest a correlation between DFP-induced increases in the levels of cerebral ACh, possibly free, and physical incapacitation.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗

PubMed1994

Mecamylamine reverses physostigmine-induced attenuation of scopolamine-induced hyperactivity.

It has previously been demonstrated that the muscarinic antagonist scopolamine induces hyperactivity in rodents, which is reversed by physostigmine but not by directly acting agonists such as pilocarpine. This may suggest that non-muscarinic actions of physostigmine may be responsible for its reversal of scopolamine-induced hyperactivity. We have found, in male Wistar rats, whose activity was measured on electromagnetic detector plates, that the central nicotinic receptor antagonist mecamylamine (3 mg/kg) reverses the blockade of scopolamine-induced behavioural activation induced by physostigmine. This suggests that activation of nicotinic receptors can counteract the effects of muscarinic blockade. Interestingly, however, treatment with nicotine does not block scopolamine-induced hyperactivity, suggesting that the exogenous and endogenous ligands may have different receptor or neuronal substrates.

Animals↗

PubMed2005

Intravenous nicotine self-administration in rats: effects of mecamylamine, hexamethonium and naloxone.

The rate and pattern of lever pressing were studied in 18 rats during 24-h sessions in which responding resulted in intravenous infusions of nicotine. There were four indications of the positive reinforcing effect of nicotine: (1) a greater number of lever presses when nicotine was response-contingent compared to when saline was available; (2) a greater number of responses on the lever resulting in an infusion of nicotine than on the control lever; (3) systematic decreases in the number of contingent nicotine infusions when nicotine was delivered noncontingently; and (4) systematic changes in the frequency of lever pressing as a function of dose. Under a fixed ratio 1 (FR 1) schedule, the number of infusions first increased and then decreased as the dose of nicotine was decreased (64, 32, 16, and 8 microg/kg infusion) and nicotine intake (mg/kg every 24 h) was directly related to the infusion dose. As the FR size was increased from 1 to 6, the number of lever presses increased and the number of infusions (32 microg/kg) remained stable. At FR values greater than 6, both the number of lever presses and infusions decreased. Presession injections of mecamylamine (0.75, 1.5, and 3.0 mg/kg, s.c.) decreased the number of infusions in a dose-related manner. Presession injections of hexamethonium (1.5 and 3.0 mg/kg, s.c.) or naloxone (0.75, 1.5, and 3.0 mg/kg, s.c.) did not alter the within- or between-session patterns of nicotine self-administration. Under the conditions of the present experiment, nicotine served as an effective reinforcer and the behavior was shown to be sensitive to both FR size and infusion dose. In addition, the results suggest that nicotine self-administration involves central nicotinic receptors and that opioid receptor antagonism has no effect on nicotine's reinforcing effects in rats.

Animals↗

PubMed1997

Nicotine-induced decreases in VTA electrical self-stimulation thresholds: blockade by haloperidol and mecamylamine but not scopolamine or ondansetron.

The effects of repeated daily injections of (-)-nicotine (+) hydrogen tartrate (mg kg-1 s.c.) on electrical self-stimulation of the ventral tegmental area were investigated. Nicotine reduced the frequency required to maintain half-maximal response rates with animals responding in rate-frequency threshold tests. Under these conditions, nicotine induced an increase in the total number of self-stimulation responses per session, but had no statistically significant effects on the maximal response rate. These effects of nicotine were observed by the second day of administration of this drug. Acute injections of the D2-like dopamine receptor antagonist haloperidol (0.03 mg kg-1 s.c.) and of the nicotinic acetylcholine receptor antagonist mecamylamine (1 mg kg-1 s.c.) attenuated the effects of nicotine, indicating that the observed effects involve stimulation of D2-like dopamine receptors as a result of nicotinic receptor activation. The muscarinic acetylcholine receptor antagonist scopolamine (3 mg kg-1 s.c.) and the serotonin 5-HT3 receptor antagonist ondansetron (0.01 and 0.1 mg kg-1 s.c.) did not alter the effects of nicotine. The results of this study indicate that repeated daily administration of (-)-nicotine increases the rewarding effects of electrical self-stimulation of the ventral tegmental area. These data are consistent with the proposal that repeated daily injections of nicotine positively effect a mesolimbic dopaminergic substrate of reward.

Animals↗

PubMed1998

Both nicotine and mecamylamine block dizocilpine-induced explosive jumping behavior in mice: psychiatric implications.

Dizocilpine (MK-801) administration to an outbred strain of NIH Swiss mice elicits discrete episodes of explosive jumping behavior designated as "popping." This behavior may serve as a useful preclinical paradigm for the screening of potentially novel antipsychotic medications. Both nicotine and mecamylamine, a nicotinic antagonist, dose-dependently blocked dizocilpine-induced popping. The data suggest that nicotine may be of therapeutic benefit in the treatment of schizophrenia and that some of its effects may be mediated by non-nicotinic receptors.

Animals↗

PubMed1991

Pretreatment with physostigmine, mecamylamine and atropine reduces the impact of soman on the cortical visual evoked potential of the cat.

A pretreatment regimen of physostigmine, mecamylamine and atropine was evaluated for its ability to alleviate the impact of soman on visual system function as measured by changes in the cortical visual evoked potential (VEP) of the cat. Data from unprotected animals showed a threshold (30% depression in the VEP) of 6.4 micrograms/kg, while in pretreated animals, the threshold dose was 32.7 micrograms/kg, yielding a protection ratio of 5:1. Extending the time between pretreatment and exposure reduced the degree of protection. Pretreatment also reduced the degree of VEP depression at suprathreshold doses, indicating a therapeutic effect even in cases of severe exposure.

Animals↗

PubMed1984

Effects of mecamylamine, nicotine, atropine and physostigmine on the phencyclidine-induced behavioral toxicity.

Phencyclidine (PCP) has multifaceted actions on the cholinergic functions, including interaction with the central and peripheral cholinergic receptors. Therefore, to evaluate the possible involvement of the nicotinic and muscarinic acetylcholine (ACh) receptors during the behavioral toxicity of PCP, influence of various cholinergic modifiers on the PCP-induced behavioral effects in male Swiss mice was studied. PCP-induced (45 mumol/kg, IP) behavioral toxicity (circular movements, side-to-side head movements, and hyperactivity leading to convulsions) was blocked by pretreating the animals with secondary- or tertiaryamino -cholinergic modifiers, mecamylamine (ME; 14.9 and 29.9 mumol/kg), nicotine (NI; 12.3 and 30.8 mumol/kg) and physostigmine (PH; 0.16 and 0.31 mumol/kg). NI at 1.5 mumol/kg significantly potentiated the PCP-induced convulsions. Atropine (AT; 14.4 and 28.8 mumol/kg) pretreatments shortened the onset of circular movements. The locomotor activity of PCP (16.4 mumol/kg) was blocked by ME, NI, and PH. AT at 7.2 mumol/kg significantly potentiated the PCP-locomotion by 62%. These observations indicated that the behavioral actions of PCP, at least in part, are mediated by the central nicotinic and muscarinic ACh receptors. The involvement of cholinergic receptors in conjunction with the dopaminergic actions of PCP during these behaviors also has been discussed.

Animals↗

PubMed1985

Methamphetamine, physostigmine, atropine and mecamylamine: effects on force lever performance.

Dose response functions for d-methamphetamine (MA), physostigmine, atropine, and mecamylamine on force lever performance (a measure of motor control) were determined in three rhesus monkeys. The rhesus monkeys were then treated with a repeated high dose regimen of MA, and the effects of the four drugs were redetermined. Following the completion of the behavioral studies, the monkeys were killed and brain monoamine concentrations were measured. It was found that each of the four drugs produced differential effects on force lever performance indices. Following the MA regimen, the MA-treated monkeys were less sensitive to the effects of MA on force lever performance but showed no change in sensitivity to any of the cholinergic agents. The monkeys were subsequently shown to have decreased brain dopamine and serotonin levels.

Animals↗

PubMed1988

Mecamylamine is a selective non-competitive antagonist of N-methyl-D-aspartate- and aspartate-induced currents in horizontal cells dissociated from the catfish retina.

The nicotinic acetylcholine channel blockers mecamylamine (MECA) and pempidine (PEMP) blocked voltage-clamped isolated catfish retina cone horizontal responses to aspartate (Asp) and N-methyl-D-aspartate (NMDA) but had little effect on currents induced by kainate and quisqualate. Concentration response curves for NMDA and Asp in the presence of MECA suggested that MECA was a non-competitive inhibitor of NMDA and Asp responses. Further, the MECA and PEMP block of NMDA and Asp-induced currents was highly voltage-sensitive. The non-competitive and voltage-sensitive block of NMDA and Asp-induced currents by MECA suggest that MECA (and PEMP) block the NMDA receptor ion channel.

Animals↗

PubMed2004

Norleucine1-Angiotensin IV alleviates mecamylamine-induced spatial memory deficits.

The brain angiotensin AT4 receptor subtype has been implicated in cognitive processing. We initially established that intracerebroventricular administration of the nAChR-antagonist mecamylamine (mec) interfered with spatial memory performance in male Sprague-Dawley rats. Next we demonstrated that mec-induced deficits in spatial memory were overcome by the AT4 receptor-agonist Norleucine1-Angiotensin IV (Nle1-Ang IV). Nle1-Ang IV could not, however, compensate for spatial learning impairments precipitated by both mec and the mAChR-antagonist scopolamine. These findings support the importance of the AT4 receptor in cognitive processing and suggest that the ability of Nle1-Ang IV to improve spatial memory deficiencies may be dependant upon the brain cholinergic system.

Angiotensin II↗

PubMed2003

Mecamylamine reduces nicotine cross-desensitization of trigeminal caudalis neuronal responses to oral chemical irritation.

We investigated the role of neuronal nicotinic acetylcholine receptors (nAChRs) in nicotine cross-desensitization of chemonociceptive responses of trigeminal subnucleus caudalis (Vc) neurons in rats. Vc responses to lingually applied pentanoic acid were significantly reduced following nicotine, and this was prevented when the nAChR antagonist mecamylamine was applied before or after nicotine. A peripheral site of nicotine cross-desensitization is suggested via a nAChR-mediated reduction in acidic excitation of lingual nociceptors that project to Vc.

Action Potentials↗