Metabolic and functional aspects of tolerance to chlormethiazole and cross‐tolerance to ethanol in the rat

Kalant, H.; Khanna, J. M.

doi:10.1111/j.1600-0447.1986.tb10535.x

Cited by 6 publications

(1 citation statement)

References 20 publications

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“…Whilst the concentration of chlormethiazole used in the medium might appear high, the IC" value for inhibition of [3H]-TPBS binding to the chloride channel is over 10-4 M and peak plasma and brain concentrations are also greater than 10-4 M following an injection of chlormethiazole of 50-100 mg kg' (Kalant & Khanna, 1986;Cross et al, unpublished observations). What the current experiments do provide is partial explanation for why chlormethiazole prevents methamphetamine-induced neurotoxicity.…”

Section: Discussionmentioning

confidence: 99%

Striatal dopamine release in vivo following neurotoxic doses of methamphetamine and effect of the neuroprotective drugs, chlormethiazole and dizocilpine

Baldwin¹,

Colado²,

Murray³

et al. 1993

British J Pharmacology

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1 Administration to rats of methamphetamine (15 mg kg-1, i.p.) every 2 h to a total of 4 doses resulted in a neurotoxic loss of striatal dopamine of 36% and of 5-hydroxytryptamine (5-HT) in the cortex (43%) and hippocampus (47%) 3 days later. 2 Administration of chlormethiazole (50mgkg-', i.p.) 15min before each dose of methamphetamine provided complete protection against the neurotoxic loss of monoamines while administration of dizocilpine (1 mg kg-', i.p.) using the same dose schedule provided substantial protection. 3 Measurement of dopamine release in the striatum by in vivo microdialysis revealed that methamphetamine produced an approximate 7000% increase in dopamine release after the first injection. The enhanced release response was somewhat diminished after the third injection but still around 4000% above baseline. Dizocilpine (1 mg kg-', i.p.) did not alter this response but chlormethiazole (50 mg kg-', i.p.) attenuated the methamphetamine-induced release by approximately 40%. 4 Dizocilpine pretreatment did not influence the decrease in the dialysate concentration of the dopamine metabolites dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) produced by administration of methamphetamine while chlormethiazole pretreatment decreased the dialysate concentration of these metabolites still further. 5 The concentration of dopamine in the dialysate during basal conditions increased modestly during the course of the experiment. This increase did not occur in chlormethiazole-treated rats. HVA concentrations were unaltered by chlormethiazole administration. 6 Chlormethiazole (100-1000IM) did not alter methamphetamine (100 tM) or K+ (35 mM)-evoked release of endogenous dopamine from striatal prisms in vitro. 7 Several NMDA antagonists prevent methamphetamine-induced neurotoxicity; however chlormethiazole is not an NMDA antagonist. Inhibition of striatal dopamine function prevents methamphetamine-induced toxicity of both dopamine and 5-HT pathways. Therefore the attenuation of the enhanced dopamine release which occurs in animals given chlormethiazole may be associated with the protective action of this drug against methamphetamine-induced neurotoxicity.

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Section: Discussionmentioning

confidence: 99%

Striatal dopamine release in vivo following neurotoxic doses of methamphetamine and effect of the neuroprotective drugs, chlormethiazole and dizocilpine

Baldwin¹,

Colado²,

Murray³

et al. 1993

British J Pharmacology

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Sonstige Psychopharmaka

Platz¹,

Böning²,

Wesemann³

et al. 1992

Neuro-Psychopharmaka

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Effect of raphe lesions on the development of acute tolerance to ethanol and pentobarbital

Campanelli

Lê²,

Khanna

et al. 1988

Psychopharmacology

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The effect of electrolytic lesions in the median and dorsal raphe nuclei was tested on acute tolerance development to ethanol and pentobarbital in the rat, as measured by motor impairment on the moving belt test. Acute tolerance to ethanol (1.7 g/kg, IP) or pentobarbital (17.5 mg/kg, IP) was monitored at 12.5, 25, or 50 min in separate subgroups tested only once each. One week of recovery was allowed between ethanol and pentobarbital tests. Median raphe lesions delayed the development of acute tolerance, whereas dorsal raphe lesions produced a negligible effect. These results were seen with both ethanol and pentobarbital. The mesolimbic 5-HT pathway from the median raphe nucleus is important in the development of acute tolerance to ethanol and pentobarbital, as was shown to be the case previously for chronic tolerance.

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Metabolic and functional aspects of tolerance to chlormethiazole and cross‐tolerance to ethanol in the rat

Cited by 6 publications

References 20 publications

Striatal dopamine release in vivo following neurotoxic doses of methamphetamine and effect of the neuroprotective drugs, chlormethiazole and dizocilpine

Striatal dopamine release in vivo following neurotoxic doses of methamphetamine and effect of the neuroprotective drugs, chlormethiazole and dizocilpine

Sonstige Psychopharmaka

Effect of raphe lesions on the development of acute tolerance to ethanol and pentobarbital

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