The pharmacology of the nicotinic antagonist, chlorisondamine, investigated in rat brain and autonomic ganglion

Clarke, Paul B. S.; Chaudieu, Isabelle; El‐Bizri, H.; Boksa, Patricia; Quik, Maryka; Esplin, Barbara; Čapek, R.

doi:10.1111/j.1476-5381.1994.tb14748.x

Cited by 61 publications

(62 citation statements)

References 45 publications

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“…Studies were initiated to determine whether activation of the autonomic ganglia after morphine administration may be involved in the elevation of plasma IL-6. Animals were pretreated with chlorisondamine, a quaternary neuronal nicotinic receptor antagonist, which has previously been shown to effectively inhibit peripheral autonomic neurotransmission (Schneider and Moore, 1955;Clarke et al, 1994). As shown in Fig.…”

Section: Resultsmentioning

confidence: 99%

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Rapid Elevation of Plasma Interleukin-6 by Morphine Is Dependent on Autonomic Stimulation of Adrenal Gland

Houghtling

Bayer²

2002

J Pharmacol Exp Ther

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Several studies have demonstrated that opioids regulate a number of immune cell functions either through direct mechanisms or through the modulation of central nervous system outputs. It has been previously shown that morphine increases serum interleukin-6 (IL-6) levels; however, the mechanism by which this effect is produced is unknown. In the present study, experiments were designed to address the potential role of central opioid receptors, peripheral autonomic ganglia, and activation of the adrenals in the elevation of plasma IL-6 after morphine administration. A rapid and significant (2-fold) increase in plasma IL-6 was observed after morphine administration (10 mg/kg s.c.) to rats. This effect of morphine peaked within 30 min and remained elevated for at least 2 h. Central microinjection of morphine (10 g/2 l i.c.v.) mimicked the effects of peripherally administered morphine and was completely blocked by naltrexone (10 mg/kg s.c.) pretreatment. Pretreatment with a ganglionic blocker, chlorisondamine (0.5 mg/kg i.p.), also blocked the elevation of IL-6 by morphine, suggesting a role of the autonomic nervous system. In adrenalectomized animals, morphine administration did not increase IL-6 levels, whereas in adrenal demedullated animals, the effect of morphine remained intact. Thus, the adrenal cortex may be a potential source of IL-6, because IL-6 mRNA has been localized in the adrenal gland. Collectively, these data suggest a unique mechanism by which stimulation of central opioid receptors results in the elevation of plasma IL-6 through autonomic activation specifically of the adrenal cortex.

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Section: Resultsmentioning

confidence: 99%

“…However, it remains to be determined whether activation of the autonomic nervous system is required for the effects of morphine on plasma IL-6 levels. To test this possibility, the bisquaternary nicotinic ganglionic receptor antagonist chlorisondamine was used to effectively inhibit peripheral autonomic neurotransmission (Clarke et al, 1994).…”

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confidence: 99%

Rapid Elevation of Plasma Interleukin-6 by Morphine Is Dependent on Autonomic Stimulation of Adrenal Gland

Houghtling

Bayer²

2002

J Pharmacol Exp Ther

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“…Moreover, two recent studies (Cohen et al, 2005;Paterson et al, 2005) have shown that GABA B agonist (CGP44532), cannabinoid (CB1) antagonist (rimonabant, SR141716), and dopamine D1 antagonist (SCH23390) reduced nicotine cue-induced recovery of nicotine-seeking responses. In addition, recent studies showing that systemic administration of nicotine increases glutamate release in ventral tegmental area (VTA) and nucleus accumbens (NAc) (Reid et al, 2000;Schilstrom et al, 2000) and that mecamylamine attenuates glutamate-mediated response (Clarke et al, 1994) suggest possible involvement of glutamatergic neurotransmission. Therefore, multiple neurotransmitter systems such as acetylcholine, dopamine, GABA, cannabinoid, and glutamate seem to be implicated in mediating this function.…”

Section: Discussionmentioning

confidence: 99%

Mecamylamine Attenuates Cue-Induced Reinstatement of Nicotine-Seeking Behavior in Rats

Liu

Caggiula

Yee

et al. 2006

Neuropsychopharmacol

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Mecamylamine, a noncompetitive nicotinic cholinergic antagonist, inhibits nicotine self-administration in animals and may attenuate tobacco smoking in humans trying to quit. Our preliminary data suggested that this agent, at a dose of 2 mg/kg (subcutaneous (s.c.)), also attenuates cue-induced relapse to nicotine-seeking behavior in rats. This study determined whether mecamylamine-induced attenuation can be obtained at doses lower than the high 2 mg/kg dose used in the first study, and whether it is specific to nicotine-associated cues. Male Sprague-Dawley rats were trained to intravenously self-administer nicotine (0.03 mg/kg/infusion) on a fixed-ratio 5 schedule. Each infusion was accompanied by a visual cue (1 s onset of a lever light followed by offset of a house light for 20 s during which time no infusions could be obtained). After the nicotine-maintained responding was extinguished by withholding the delivery of nicotine (saline substitution) and its associated cue, reinstatement tests were conducted. Response-contingent re-presentation of the cue without further availability of nicotine significantly reinstated extinguished responding at the previously nicotine-reinforced lever. Pretreatment with mecamylamine (0.5, 1, and 2 mg/kg, s.c.) dose-dependently attenuated the cue-induced reinstatement of lever responding. Mecamylamine did not change food-taking and -seeking responses, whereas the highest dose (2 mg/kg) decreased nicotine selfadministration behavior. The results confirm previous findings that stimuli conditioned to nicotine self-administration effectively elicit reinstatement of nicotine-seeking behavior after extinction and demonstrate that mecamylamine, besides suppressing self-administration of nicotine, effectively attenuates cue-induced nicotine-seeking behavior. These findings suggest that the response-reinstatement procedures used in this study may be useful for studying neurobiological mechanisms of nicotine-seeking behavior and that mecamylamine-like drugs may be potential candidates for pharmacological treatment and prevention of relapse to tobacco smoking in abstinent smokers.

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“…The bisquaternary structure of CHL appears to impede passage across the blood brain barrier, but a single administration of the drug, given either directly into the cerebral ventricles or in a sufficiently high dose systemically, results in a pharmacologically selective and remarkably persistent (several weeks) blockade of central actions of nicotine (Clarke & Kumar, 1983;Clarke, 1984;Reavill et al, 1986;Fudala & Iwamoto, 1987;Kumar et al, 1987;Mundy & Iwamoto, 1988;Clarke & Fibiger, 1990;Corrigall et al, 1992;Clarke et al, 1994). In contrast, ganglionic blockade induced by CHL is transient (Grimson et al, 1955;Plummer et al, 1955;Schneider & Moore, 1955;Clarke et al, 1994).…”

Section: Introductionmentioning

confidence: 99%

Blockade of nicotinic receptor‐mediated release of dopamine from striatal synaptosomes by chlorisondamine and other nicotinic antagonists administered in vitro

El‐Bizri

Clarke

1994

British J Pharmacology

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1 Central nicotinic receptor function examined in vitro, by measuring nicotine-induced [3H]-dopamine release from rat striatal synaptosomes.2 The agonists (-)-nicotine, acetylcholine, 1,1-dimethyl-4-phenylpiperazinium (DMPP) and cytisine (10-7-10-4 M) all increased [3H]-dopamine release in a concentration-dependent manner. Cytisine did not produce a full agonist response, compared to the other agonists. 3 The actions of nicotine, acetylcholine and cytisine were largely dependent on external Ca2". In contrast, DMPP (l0-s and 10-4 M) evoked a marked release of [3H]-dopamine even in the absence of Ca2". Nevertheless, in the presence of external Ca2", responses to DMPP were completely blocked by the nicotinic antagonists chlorisondamine and mecamylamine (5 x 1-0 M); in the absence of external Ca2", blockade was only partial. 4 Chlorisondamine, mecamylamine and dihydro-p-erythroidine (l0-8-0-4 M) produced a concentration-dependent block of responses to nicotine (10-6 M). Approximate ICm values were 1.6, 0.3 and 0.2 x 10-6, respectively. Chlorisondamine and mecamylamine blocked responses to nicotine (107-10-4 M) insurmountably, whereas dihydro-p-erythroidine behaved in a surmountable fashion.5 The occurrence of use-dependent block was tested by briefly pre-exposing the synaptosomes to nicotine during superfusion with antagonist, and determining the response to a subsequent nicotine application. Consistent with a possible channel blocking action, brief pre-exposure to agonist increased the antagonist potency of chlorisondamine (approximately 25 fold). No significant use-dependent block was detected with dihydro-p-erythroidine.

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The pharmacology of the nicotinic antagonist, chlorisondamine, investigated in rat brain and autonomic ganglion

Cited by 61 publications

References 45 publications

Rapid Elevation of Plasma Interleukin-6 by Morphine Is Dependent on Autonomic Stimulation of Adrenal Gland

Rapid Elevation of Plasma Interleukin-6 by Morphine Is Dependent on Autonomic Stimulation of Adrenal Gland

Mecamylamine Attenuates Cue-Induced Reinstatement of Nicotine-Seeking Behavior in Rats

Blockade of nicotinic receptor‐mediated release of dopamine from striatal synaptosomes by chlorisondamine and other nicotinic antagonists administered in vitro

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