A randomized controlled trial of oral selegiline plus nicotine skin patch compared with placebo plus nicotine skin patch for smoking cessation

Biberman, R.; Neumann, R.; Katzir, Itzhak; Gerber, Yariv

doi:10.1046/j.1360-0443.2003.00524.x

Cited by 67 publications

(39 citation statements)

References 9 publications

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“…These data were not repro-duced when investigated in a larger patient cohort where no improvement over placebo was observed (Weinberger et al, 2010). Similarly, a study with 108 participants in Israel also failed to demonstrate superiority over placebo (Biberman, Neumann, Katzir, & Gerber, 2003). A transdermal patch of selegiline in combination with cognitive behaviour training treating 243 adult smokers also did not show a statistical difference to placebo (Killen et al, 2010).…”

Section: Smokingmentioning

confidence: 84%

Monoamine Oxidase Inhibitors—Revisiting a Therapeutic Principle

Entzeroth¹,

Ratty²

2017

OJD

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Over more than 60 years, monoamine oxidase (MAO) inhibitors are available for therapy of central nervous diseases. Although they have shown to be efficacious specifically in the treatment of major depressive disorders and treatment-resistant depression, they became less a therapeutic choice for the physicians mostly due to severe side effects, such as liver failure and hypertensive crisis associated specifically with the first generation of inhibitors. Nevertheless, this class of drugs is still being used for treatment specifically as more selective and reversible inhibitors became available and will provide clinicians with additional treatment options. The current review revisits monoamine oxidase inhibitors and their potential in the treatment of human diseases, such as anxiety, depression, mood and personality disorders, and pain and introduces current ideas and developments.

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Section: Smokingmentioning

confidence: 84%

Monoamine Oxidase Inhibitors—Revisiting a Therapeutic Principle

Entzeroth¹,

Ratty²

2017

OJD

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“…htm). Previous studies demonstrated that selegiline was an effective aide in smoking cessation (Biberman et al, 2003;George et al, 2003). At least four clinical trials are currently underway to evaluate the effectiveness of selegiline as a potential therapy in smoking cessation (http://www.…”

Section: Discussionmentioning

confidence: 99%

“…oral selegiline increased the trial endpoint (8-week) 7-day point prevalent abstinence compared with placebo by 3-fold (George et al, 2003). In a third study that used a combination of oral selegiline and nicotine patch, selegiline plus nicotine patch doubled the 52-week continuous abstinence rate compared with nicotine patch alone, although the difference was not significant due to small subject numbers (Biberman et al, 2003). Other MAO inhibitors have also been investigated for their effects on smoking cessation, but due to poor efficacy (moclobemide) or toxicity (lazabemide), they are no longer studied (McRobbie et al, 2005).…”

mentioning

confidence: 99%

Selegiline Is a Mechanism-Based Inactivator of CYP2A6 Inhibiting Nicotine Metabolism in Humans and Mice

Siu¹,

Tyndale²

2007

J Pharmacol Exp Ther

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Selegiline (L-deprenyl) is in clinical treatment trials as a potential smoking cessation drug. We investigated the affect of selegiline and its metabolites on nicotine metabolism. In mice, selegiline was a potent inhibitor of nicotine metabolism in hepatic microsomes and cDNA-expressed CYP2A5; the selegiline metabolites desmethylselegiline, L-methamphetamine, and L-amphetamine, also inhibited nicotine metabolism. Pretreatment with selegiline and desmethylselegiline increased inhibition (IC 50 ) in microsomes by 3.3-and 6.1-fold, respectively. In mice in vivo, selegiline increased AUC (90.7 Ϯ 5.8 versus 57.4 Ϯ 5.3 ng/h/ml, p Ͻ 0.05), decreased clearance (4.6 Ϯ 0.4 versus 7.3 Ϯ 0.3 ml/min, p Ͻ 0.05), and increased elimination half-life (12.5 Ϯ 6.3 versus 6.6 Ϯ 1.4 min, p Ͻ 0.05) of nicotine. In vitro, selegiline was a potent inhibitor of human nicotine metabolism in hepatic microsomes and cDNA-expressed CYP2A6; desmethylselegiline and L-amphetamine also inhibited nicotine metabolism. Selegiline preincubation increased inhibition in microsomes (3.7-fold) and CYP2A6 (14.8-fold); the K i for CYP2A6 was 4.2 M. Selegiline dose-and time-dependently inhibited nicotine metabolism by CYP2A6 (K I ϭ 15.6 Ϯ 2.7 M; k inact ϭ 0.34 Ϯ 0.04 min Ϫ1 ), and the inhibition was irreversible in the presence of NADPH, indicating that it is a mechanism-based inhibitor of CYP2A6. Thus, inhibition of mouse nicotine metabolism by selegiline was competitive in vitro and significantly increased plasma nicotine in vivo. In humans, where selegiline is both a competitive and mechanismbased inhibitor, it is likely to have even greater effects on in vivo nicotine metabolism. Our findings suggest that an additional potential mechanism of selegiline in smoking cessation is through inhibition of nicotine metabolism.

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“…[7][8][9][10]12 In our selegiline clinical trial, overall the drug had no effect on any of the primary outcome measures. 11 However, the present pharmacogenetic analysis of the same clinical dataset revealed several significant results.…”

Section: Discussionmentioning

confidence: 99%

“…8 A randomized double-blind placebo-controlled trial of oral selegiline plus NRT in 109 smokers reported an association between selegiline and reduced craving. 9 In contrast, another study of comparable design and similar size showed no effect of oral selegiline on craving or abstinence. 10 We recently performed the first trial of transdermal selegiline for smoking cessation.…”

Section: Introductionmentioning

confidence: 94%

Response to Transdermal Selegiline Smoking Cessation Therapy and Markers in the 15q24 Chromosomal Region

Sarginson

Killen

Lazzeroni

et al. 2015

NICTOB

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Introduction: Current treatments for smoking cessation have limited efficacy. A potential pharmaceutical treatment for smoking cessation is selegiline, a selective and irreversible monoamine oxidase B inhibitor. A few clinical trials have been carried out using selegiline but the results have been mixed. We sought to determine if genetic markers in cholinergic loci in the 15q24 chromosomal region predict response to smoking cessation therapy with selegiline. Methods: We performed an 8-week double-blind, placebo-controlled clinical trial of the selegiline transdermal system in heavy smokers, with follow-up at weeks 25 and 52. Eight single nucleotide polymorphisms (SNPs) in the 15q24 region, which contains the genes for the nicotinic acetylcholine receptor subunits CHRNA5, CHRNA3, and CHRNB4, were investigated for association with treatment response. Results: The CHRNB4 promoter SNP rs3813567 was associated with both point prevalence abstinence and post-quit craving. Carriers of the minor C allele treated with selegiline showed lower rates of abstinence and higher levels of craving than selegiline-treated non-carriers, indicating that the rs3813567 C allele adversely affects abstinence in selegiline-treated smokers. This effect was not present among placebo-treated smokers. Selegiline-treated smokers with the CHRNA5 rs680244 GG genotype had lower post-quit craving, and unlike placebo-treated GG-carrying smokers, did not experience a post-quit increase in depressive symptoms. Conclusions: Variants in genes encoding cholinergic receptors affect abstinence, craving and mood in selegiline-treated smokers. Selegiline primarily affects dopamine levels in the brain, but cholinergic input affects nicotine-induced dopaminergic activity. These markers may have value in identifying those likely to respond to selegiline for smoking cessation.

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A randomized controlled trial of oral selegiline plus nicotine skin patch compared with placebo plus nicotine skin patch for smoking cessation

Cited by 67 publications

References 9 publications

Monoamine Oxidase Inhibitors—Revisiting a Therapeutic Principle

Monoamine Oxidase Inhibitors—Revisiting a Therapeutic Principle

Selegiline Is a Mechanism-Based Inactivator of CYP2A6 Inhibiting Nicotine Metabolism in Humans and Mice

Response to Transdermal Selegiline Smoking Cessation Therapy and Markers in the 15q24 Chromosomal Region

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