The comparative binding characteristics of nicotinic ligands and their pharmacology

Sloan, Jewell W.; Martin, William R.; Bostwick, M.; Hook, Robert; Wala, Elzbieta P.

doi:10.1016/0091-3057(88)90454-6

Cited by 54 publications

(32 citation statements)

References 22 publications

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“…[100][101][102][103][104] Although lobeline has no structural resemblance to nicotine, and SARs do not suggest a common pharmacophore, 105 it has many nicotinelike effects, such as tachycardia and hypertension, 106 bradycardia and hypotension in anesthetized rats, 107 anxiolytic activity, 108 and improvement of learning and memory. 109 In contrast to nicotine, lobeline only marginally supports selfadministration in mice 110 and does not support self-administration in rats.…”

Section: Lobeline and Its Analogsmentioning

confidence: 99%

Vesicular monoamine transporter 2: Role as a novel target for drug development

Zheng

Dwoskin

Crooks

2006

AAPS J

105

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Section: Lobeline and Its Analogsmentioning

confidence: 99%

Vesicular monoamine transporter 2: Role as a novel target for drug development

Zheng

Dwoskin

Crooks

2006

AAPS J

105

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“…The antagonists used were mecamylamine (Stone et al, 1956;Martin et al, 1989), a nicotine receptor ion channel blocker that is uncompetitive in its actions, and dihydro-␤-erythroidine (DH␤E) (Williams and Robinson, 1984;Sabey et al, 1999;Shoaib et al, 2000), a competitive, ␣4␤2-selective nicotine antagonist. The partial agonists were varenicline (Coe et al, 2005) and cytisine (Barlow and McLeod, 1969;Romano et al, 1981;Sloan et al, 1988). Interaction studies were performed in rats trained to discriminate between saline and a large or a small dose of nicotine.…”

Section: Introductionmentioning

confidence: 99%

Patterns of Nicotinic Receptor Antagonism: Nicotine Discrimination Studies

Jutkiewicz¹,

Brooks²,

Kynaston³

et al. 2011

J Pharmacol Exp Ther

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Evaluation of the discriminative stimulus effects of drugs is a useful procedure for identification of receptor mediation of in vivo drug effects. This assay can be enhanced when the stimulus effects of different doses of agonist are evaluated. In the present study, rats were trained to discriminate small or large doses of nicotine from saline, and interactions of these effects with nicotinic receptor antagonists and partial agonists were determined. The insurmountable nicotine antagonist mecamylamine blocked both the discriminative stimulus and response rate-reducing effects of nicotine but was less effective against the large dose of nicotine. The ␣4␤2*-selective, competitive antagonist dihydro-␤-erythrodine (DH␤E) antagonized the discriminative stimulus effects of both doses but was less effective against the larger training dose of nicotine. Schild analyses of DH␤E suggested that different nicotinic receptor populations may be mediating the stimulus effects of large and small doses of nicotine. This suggestion was supported by observations that the discriminative stimulus effects of the partial agonist cytisine were more like those of the large dose than of the small dose of nicotine and that cytisine antagonized the effects of only the small nicotine dose. Varenicline produced nicotine-like effects in both training dose groups but reduced the discriminative stimulus effects of intermediate doses of nicotine in the group trained to the small dose of nicotine. Overall, these results suggest that small doses of nicotine produce their stimulus effects via ␣4␤2* nicotine receptors, whereas larger doses of nicotine recruit additional nicotine receptor subtypes, as revealed by drug discrimination assays in rats.

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“…Poisoning by anabasine is characterized by nicotine-like toxicity. The clinical effects of nicotine alkaloid toxicity are the result of the summation of actions at ganglionic sites, motor end plates, and smooth muscle [17,18,[21][22][23]. Nicotine alkaloids initially stimulate the ganglia of the sympathetic and parasympathetic nervous systems by direct cholinomimetic action on the ganglia.…”

Section: Discussionmentioning

confidence: 99%

“…The present case is consistent with this pattern of nicotinic intoxication with vomiting and dizziness developing 30 min after ingestion, followed by a respiratory arrest after about 90 min. There is no antidote for nicotinic cholinergic poisoning, and the treatment is largely supportive and symptomatic [17,18].…”

Section: Discussionmentioning

confidence: 99%

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Nicotiana glauca (Tree Tobacco) Intoxication—Two Cases in One Family

et al. 2010

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We present two cases of rare human poisoning in one family following ingestion of cooked leaves from the tobacco tree plant, Nicotiana glauca. The toxic principle of N. glauca, anabasine (C10H14N2), is a small pyridine alkaloid, similar in both structure and effects to nicotine, but appears to be more potent in humans. A 73-year-old female tourist from France, without remarkable medical history, collapsed at home following a few hours long prodrome of dizziness, nausea, vomiting, and malaise. The symptoms developed shortly after eating N. glauca cooked leaves that were collected around her daughter's house in Jerusalem and mistaken for wild spinach. She was found unconscious, with dilated pupils and extreme bradycardia. Following resuscitation and respiratory support, circulation was restored. However, she did not regain consciousness and died 20 days after admission because of multi-organ failure. Anabasine was identified by gas chromatography/mass spectrometry method in N. glauca leaves and in the patient's urine. Simultaneously, her 18-year-old grandson developed weakness and myalgia after ingesting a smaller amount of the same meal. He presented to the same emergency room in a stable condition. His exam was remarkable only for sinus bradycardia. He was discharged without any specific treatment. He recovered in 24 h without any residual sequelae. These cases raise an awareness of the potential toxicity caused by ingestion of tobacco tree leaves and highlight the dangers of ingesting botanicals by lay public. Moreover, they add to the clinical spectrum of N. glauca intoxication.

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The comparative binding characteristics of nicotinic ligands and their pharmacology

Cited by 54 publications

References 22 publications

Vesicular monoamine transporter 2: Role as a novel target for drug development

Vesicular monoamine transporter 2: Role as a novel target for drug development

Patterns of Nicotinic Receptor Antagonism: Nicotine Discrimination Studies

Nicotiana glauca (Tree Tobacco) Intoxication—Two Cases in One Family

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