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Results for “MECAMYLAMINE”

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At least 163 records · Page 9Linked to original sources

PubMed1998

Nitric oxide mediates mecamylamine- and naloxone-precipitated nicotine withdrawal.

A nitric oxide synthase inhibitor blocked nicotine abstinence signs and increased weight loss in male, nicotine-dependent rats during withdrawal precipitated by the nicotinic receptor antagonist mecamylamine or the opioid receptor antagonist naloxone. These results indicate that nitric oxide systems mediate important aspects of the expression of nicotine physical dependence and suggest the potential use of nitric oxide synthase inhibitors as aids in tobacco smoking cessation.

Animals↗

PubMed1987

Mecamylamine prevents the enhancement of retention induced by lysine vasopressin in mice.

Lysine vasopressin (0.03 microgram/kg, sc) enhanced retention of a one-trial, step-through inhibitory avoidance task when injected into male Swiss mice immediately post-training, as indicated by retention performance 48 h later. A low dose of the vasopressin antagonist, AAVP (0.01 microgram/kg, sc), did not significantly affect retention, whereas a higher dose (0.03 microgram/kg, sc) impaired retention. Neither lysine vasopressin nor AAVP modified latencies to step-through of mice that had not received a footshock during training. The simultaneous injection of AAVP (0.01 microgram/kg, sc) prevented the enhancement of retention induced by lysine vasopressin. The influence of lysine vasopressin on retention was antagonized by the simultaneous administration of mecamylamine (5 mg/kg, sc) but not by hexamethonium (5 mg/kg, sc), atropine (0.5 mg/kg, sc), or methylatropine (0.5 mg/kg, sc). A modulatory role of vasopressin on the activity of central cholinergic nicotinic mechanisms which participate in memory formation is suggested.

Animals↗

PubMed2000

Mecamylamine but not the alpha7 receptor antagonist alpha-bungarotoxin blocks sensitization to the locomotor stimulant effects of nicotine.

The involvement of alpha7 receptors in the locomotor stimulant effects of nicotine has been examined by determining the ability of intracerebroventricular (i.c.v.) administration of the alpha7 receptor antagonist alpha-bungarotoxin (alpha-bgt) to modify sensitization to the locomotor activating effects of chronic nicotine. Intracerebroventricular administration of alpha-bgt (0.02 - 8 nmoles) produced a dose dependent increase in convulsive behaviour. At doses less than 1.0 nmole, minimal convulsive behaviour occurred but larger doses evoked convulsions in all rats which displayed a more rapid onset time as the dose increased. The binding distribution of alpha7 receptors 20 min and 3 h following an i.c.v. administration of [(125)I]-alpha-bgt (0.02 nmoles) revealed clear binding in the hippocampus, cingulate cortex and hypothalamus which was more intense after 3 h. Rats chronically treated with nicotine (0.4 mg kg(-1)) and exposed to the locomotor activity apparatus daily acquired an increase in locomotor activity relative to the control group after 3 days of treatment which reached a maximum after 7 days of treatment and was maintained for the 2 week treatment period. Pre-treatment with mecamylamine (1 mg kg(-1)) prevented the expression of the locomotor stimulant effects of nicotine but pre-treatment with i.c.v. alpha-bgt (0.02 nmoles) did not affect nicotine-induced changes in locomotor activity. The results of this study support the conclusion that nicotinic receptors of the alpha4beta2 subtype rather than the alpha7 subtype are important in mediating the expression of the locomotor stimulant effects of nicotine.

Animals↗

PubMed1984

Influence of mecamylamine and atropine on tolerance development to nicotine hypothermia in rats.

Nicotine hypothermia is known as a central effect of nicotine waning after repeated administration due to the development of tolerance. In the present experiments using female rats, this tolerance was attenuated by the concomitant administration of mecamylamine. Atropine was without effect. It is concluded that tolerance to this effect of nicotine implies its contact with specific sites within the cns.

Animals↗

PubMed1999

Mecamylamine blocks the [Asp1,Val5]-ANG II-induced attenuation of salt gland activity in Pekin ducks.

An intravenous injection of 2 microg of [Asp1,Val5]-ANG II attenuated fluid secretion by the nasal salt glands of Pekin ducks. Ganglionic blockade with mecamylamine stopped salt gland secretion. Flow was reestablished by intravenous methacholine bromide during ganglionic blockade. A second injection of 2 microg of [Asp1, Val5]-ANG II failed to attenuate secretion during ganglionic blockade, showing that the peptide acts via the central nervous system and postganglionic parasympathetic nerves that supply the salt glands. Sympathetic nerves are located in the walls of blood vessels within the salt glands, and adrenergic fibers with "varicosities" supply extensively the secretory tubules. [Asp1, Val5]-ANG II decreased salt gland secretion both before and after alpha1-adrenergic blockade with prazosin, showing that the lowered activity was not caused by the release of norepinephrine from nerve endings and/or duck adrenal chromaffin cells. beta-Adrenergic blockade with propranolol also failed to prevent the attenuation of secretion in response to an intravenous injection of 2 microg of [Asp1,Val5]-ANG II, which showed that epinephrine did not mediate the response to the peptide.

Adrenergic alpha-Antagonists↗

PubMed1986

Mecamylamine, but not atropine, antagonizes nicotine-induced hyperglycemia and potentiation of hypnosis produced by pentobarbital in mice.

An anesthetic dose of 50 mg/kg (i.p.) sodium pentobarbital caused a 61% increase in blood glucose levels in mice. Nicotine (2.5 mg/kg) given intraperitoneally 15 min prior to the sodium pentobarbital treatment further increased hyperglycemia by 29% over pentobarbital alone and 90% higher than the control. Mecamylamine (0.5 mg/kg) given intraperitoneally 15 min prior to nicotine resulted in blood glucose concentrations near the control value. Atropine (2 mg/kg) administered intraperitoneally did not prevent the hyperglycemia induced by nicotine and pentobarbital. No significant correlation was observed between the sleep time and the blood glucose of the unconscious or awake mice. However, a significant correlation was observed between the blood glucose concentration of the sleeping and awake mice. Blood glucose levels were always higher when the neuronal activity was depressed and were lower when the neuronal activity was increased.

Animals↗

PubMed2002

[Difference in action sites between mecamylamine and hexamethonium on nicotinic receptors of sympathetic neurons].

To compare the difference in action sites between mecamylamine (MEC) and hexamethonium (HEX) on nicotinic receptors of sympathetic neurons, we investigated the effects of MEC and HEX on the nicotine-induced currents in cultured superior cervical ganglion neurons by whole-cell patch clamp technique. The IC(50) of MEC and HEX for antagonizing the effect of 0.08 mmol/L nicotine was 0.0012 and 0.0095 mmol/L, respectively. Both MEC and HEX accelerated the desensitization of nicotinic receptors. Furthermore, by comparing their effects at holding potentials 30, 70 and 110 mV, it was indicated that their suppressing effect on the nicotine-induced currents was voltage-dependent. However, different from that of HEX, the inhibitory effect of MEC increased with administering the mixture of MEC and nicotine at intervals of 3 min, indicating a use-dependent effect of MEC. It is concluded that the action site of MEC on nicotinic receptors of sympathetic neurons is different from that of HEX.

Animals↗

PubMed2006

Mecamylamine (Targacept).

Targacept Inc, under license from the University of South Florida, is developing a low-dose, liquid gel capsule formulation of the nicotinic acetylcholine antagonist mecamylamine, as a potential treatment for various neuropsychiatric disorders.

Adolescent↗

PubMedDate not supplied

Effects of atropine and mecamylamine given locally into periaqueductal gray on bioelectrical activity of chosen brain structures of the rabbit.

Atropine (Atr) or mecamylamine (MeC) were administered locally into the periaqueductal gray (PAG) of rabbits with chronically implanted electrodes into the motor-sensory cortex (MSC) ventro-posterolateral thalamic nuclei (NVPL), PAG and midbrain reticular formation (MRF). Bioelectrical responses in the cortex and subcortical structures were analyzed automatically by means of Fast Fourier Transform and Autoregressive Method. Both Atr and Mec modified the activity in PAG, Atr had also the influence in MRF and MSC.

Animals↗

PubMed1984

Clinical evaluation of mecamylamine for withdrawal from nicotine dependence.

Mecamylamine (MCL) has been shown to extinguish nicotine dependence in rats and monkeys. MCL was administered to fourteen nicotine-dependent persons to determine if it may be effective in withdrawing nicotine-dependent humans at doses which have acceptable toxicity. Subjects smoked 20 to 60 cigarettes per day for a mean of 2.4 years, and none had been nicotine abstinent for as much as one day for at least one year. MCL was started in a dose of 5 to 10 mg per day and progressively raised until the subject experienced nicotine blockage and/or toxic effects. During MCL administration, 7 of 14 (50%) totally ceased smoking within the first 11 days of treatment, and an additional 4 (28.6%) subjects reduced cigarette consumption to less than five per day by the end of three weeks. Thirteen of 14 (92.9%) subjects stated that MCL blocks nicotine, reduces nicotine craving, and "works." At least some minor side-effects of MCL were observed in every subject. The most intolerable side-effects were constipation, urinary retention, abdominal cramps, and weakness, and these were responsible for drop-out of 5 (35.7%) subjects. Although there is a high prevalence of side-effects, MCL is probably a viable withdrawal treatment for some cases of recalcitrant nicotine dependence.

Adult↗

PubMed1984

Withdrawal from nicotine dependence using mecamylamine: comparison of three-week and six-week dosage schedules.

Mecamylamine (MCL) has been shown to extinguish nicotine dependence in animals and produce smoking cessation in some humans. This study was done to determine if MCL may be more effective and have fewer side-effects when administered at low dosages over a six-week period than at high dosages given over a three-week period. Subjects in the high-dose, three-week group demonstrated significantly more reduction of nicotine intake as evidenced by self-report and presence of nicotine in urine although side-effects were more pronounced. Although MCL's numerous side-effects should limit its clinical use to recalcitrant smokers who have failed other types of treatment, its nicotine antagonist property indicates it can be an effective agent to withdraw some persons from nicotine dependence.

Adult↗

PubMed1995

[Nicotinic currents of cultured rat superior cervical ganglion neurons and use-dependent block by mecamylamine].

AIM: Comparison of action of nicotinic agonists and antagonists on nicotinic acetylcholine receptor (nAChR) in superior cervical ganglion (SCG) neurons. METHODS: Whole-cell recordings were made from cultured neonatal rat SCG neurons. Cholinergic drugs were applied by local pressure perfusion. RESULTS: The neurons were activated by nicotinic agonists and peak current were acetylcholine (ACh), 443 +/- 183 pA; nicotine, 1175 +/- 377 pA; dimethylphenylpiperazinium (DMPP), 2946 +/- 358 pA, respectively. The nicotinic responses were blocked by mecamylamine (Mec), hexamethonium and curare, the efficacies were 435 +/- 154 pA, 725 +/- 320 pA, 887 +/- 214 pA, but not by alpha-bungarotoxin. The block by Mec was use-dependent, i.e., it was dependent on repeated presentation of the agonists. The first 6 peak currents were expressed as percentage of the first response as following: 100, 64 +/- 3, 50 +/- 3, 41 +/- 4, 32 +/- 3%. CONCLUSION: The present data suggest that nAChR of SCG neurons have different pharmacological characteristics from that of muscle or central neurons.

Animals↗

PubMed1998

Effects of nicotine and mecamylamine microinjections into the nucleus accumbens on ethanol and sucrose self-administration.

Nicotine (NIC) and ethanol (ETOH) are both drugs of abuse that can affect similar pathways in the central nervous system. However, the role of nicotinic processes in ETOH's reinforcing actions is unclear. Although the mesolimbic dopamine systems are known to be involved in the reinforcing effects of ETOH, the role of nicotinic receptors within the nucleus accumbens (NAc) in ETOH reinforcement has not been studied. To address this issue, adult male Long-Evans rats were initiated to self-administer ETOH (10% v/v, n = 14) using the sucrose-substitution procedure or sucrose (5% w/v, n = 8) in a 30-min operant session. They were then surgically implanted with bilateral stainless-steel guide cannulae to allow for microinjection into the core of the NAc. After recovery from surgery, presession microinjections of NIC (0.3, 3.3, 10, 30, and 60 microg/1 microl/brain) or the antagonist mecamylamine (MEC) (1, 3, 10, 30, and 60 microg/1 microl/brain) were performed prior to an ETOH or sucrose self-administration session. NIC (3.3 and 60 microg/microl) and MEC (30 microg/microl) both reduced ETOH self-administration behavior, without affecting sucrose-reinforced behavior. A reduction in the total duration of ETOH responding (termination) was also observed after either 60 microg/microl of NIC and 30 microg/microl of MEC. The lack of a clear dose-response relationship for the agonist and the antagonist indicates that the interaction between the NAc nicotinic system and ETOH self-administration is complex.

Acetylcholine↗

PubMed1963