Modification of nicotine toxicity by pretreatment with different drugs

Barrass, B. C.; Blackburn, Jeff; Brimblecombe, R. W.; Rich, Preston B.

doi:10.1016/0006-2952(69)90319-0

Cited by 20 publications

(6 citation statements)

References 4 publications

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“…Interestingly, Spealman and Goldberg, in a 1982 study of schedule-controlled behavior by intravenous injections of nicotine in squirrel monkeys, reported a similar finding; doses on the order of 300 gg/kg usually produced vomiting in these monkeys even at very low levels of responding, whereas in combination with mecamylamine, vomiting was not seen. These findings suggest that mecamylamine successfully blocked nicotininic cholinergic mechanisms involved in nicotine-induced nausea and vomiting and raise the question of whether exposure to potentially toxic levels of nicotine in the absence of normal selflimiting feedback mechanisms constitutes an added riskalthough hexamethonium, a quaternary ganglionic blocker, and pempidine, like mecamylamine a tertiary compound, seem to confer protection from nicotine toxicity in mice (Barrass et al 1969).…”

Section: Discussionmentioning

confidence: 93%

Mecamylamine pretreatment increases subsequent nicotine self-administration as indicated by changes in plasma nicotine level

Pomerleau

Majchrzak

1987

Psychopharmacology

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Acute administration of mecamylamine, a centrally active nicotinic cholinergic agonist, has been shown to increase amount of smoking as indicated by smoking topography (e.g., puff rate, puff duration), expired carbon monoxide changes, and other inferential measures. In the present study, subjects showed significantly greater increases in plasma nicotine following smoking of two high-nicotine research cigarettes when pretreated with mecamylamine than when pretreated with placebo, even though no significant differences in puff volume or puff number were detected. Interestingly, none of our subjects reported nausea, although some achieved plasma nicotine levels at which nausea would typically be expected. We attribute the observed increases in nicotine intake to compensatory behavior designed to overcome mecamylamine's blocking effects.

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Section: Discussionmentioning

confidence: 93%

Mecamylamine pretreatment increases subsequent nicotine self-administration as indicated by changes in plasma nicotine level

Pomerleau

Majchrzak

1987

Psychopharmacology

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“…This develops and subsides within minutes or hours of a single injection. Acute tolerance has also been reported in tests of antinociception (Tripathi et al 1982) and lethality (Barrass et al 1969). Acute tolerance may underlie the rapid development of tolerance to nicotine's locomotor stimulant action when the drug is continuously infused (Cronan et al 1985).…”

Section: Tolerancementioning

confidence: 98%

Nicotine and smoking: a perspective from animal studies

Clarke

1987

Psychopharmacology

131

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Nicotine plays a key role in reinforcing tobacco smoking, and exerts several psychoneuropharmacological actions which may contribute to its reinforcing effects. Thus, nicotine can improve mood and alleviate withdrawal symptoms; it can also alter CNS arousal, reduce stress, suppress appetite, and improve performance on certain tasks. Behavioural studies in animals have tended to corroborate existing theories of smoking behaviour, and have started to suggest how and where nicotine may exert its central actions in man. Clinical evidence suggests that smoking cessation would be facilitated by the administration of a nicotinic antagonist having a selective action on central nicotinic cholinoceptors of the C6 (ganglionic) type. Pharmacological studies in animals indicate that such a drug is a reasonable prospect.

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“…In experiments designed to investigate the mechanism of these phenomena (44), it was found that the reduction product of cotinine with lithium aluminium hydride displayed protection. This reduction product, which could not be isolated, was thought to be 5'-hydroxynicotine.…”

Section: Pharmacological and Toxicological Consequencesmentioning

confidence: 99%

The metabolism of alicyclic amines to reactive iminium ion intermediates

Gorrod

Aislaitner

1994

Eur. J. Drug Metab. Pharmacokinet.

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The evidence implicating the formation of iminium ions as reactive intermediates in the metabolism of alicyclic amines has been reviewed. The mechanism of formation of iminium ions and their conversion to alpha-carbonyl compounds or demethylated amines is discussed. The use of a simple cyanide trapping technique for iminium ions has been demonstrated to monitor a large number of alicyclic drugs for iminium ion formation. The possible role of iminium ions in the pharmacology and toxicology of alicyclic amines is considered.

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Modification of nicotine toxicity by pretreatment with different drugs

Cited by 20 publications

References 4 publications

Mecamylamine pretreatment increases subsequent nicotine self-administration as indicated by changes in plasma nicotine level

Mecamylamine pretreatment increases subsequent nicotine self-administration as indicated by changes in plasma nicotine level

Nicotine and smoking: a perspective from animal studies

The metabolism of alicyclic amines to reactive iminium ion intermediates

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