Varenicline

Varenicline is a partial agonist/antagonist of α4β2 nicotinic acetylcholine receptor [1].

Varenicline is a manufactured tartrate salt, it is a partial agonist of α4β2 nAChRs. The affinity(0.15 nM) of varenicline with α4β2 nAChRs is much more higher than with other nAChR subtypes. Through the binding, varenicline prevents nicotine from occupying the receptors and subsequently inhibit nicotine-induced dopaminergic activation. So varenicline is used for smoking cessation. In healthy adult smokers, varenicline does not undergo significant hepatic metabolism and the clearance(>90%) is predominantly renal. It is shown that the amphetamine administration may have decrease the efficacy of varenicline [1].

References:
[1] Garrison GD, Dugan SE. Varenicline: a first-line treatment option for smoking cessation. Clin Ther. 2009 Mar;31(3):463-91.

The effect of varenicline and nicotine patch on smoking rate and satisfaction with smoking: an examination of the mechanism of action of two pre-quit pharmacotherapies.[Pubmed:28342090]

Psychopharmacology (Berl). 2017 Jul;234(13):1969-1976.

OBJECTIVES: In recent years, there has been growing research interest in using nicotine replacement medications to aid smoking reduction prior to a quit attempt. Gaining a better understanding of how treatments influence smoking reduction may allow for better tailoring of treatments and, ultimately, better cessation outcomes. The objective of the current study was to test the effects of the pre-quit use of Varenicline and nicotine patch on smoking rate and satisfaction with smoking. METHODS: All participants were required to attend up to five study visit sections. Participants (n = 213) who were interested in quitting were randomised (open-label) to receive either pre-quit patch or Varenicline (both treatments started 2 weeks prior to an assigned quit day, followed by 10 weeks post-quit) or standard patch (10 weeks starting from an assigned quit day). Participants used modified smartphones to monitor their smoking in real time for 4 weeks. RESULTS: Participants in the two pre-quit treatment groups reported significant reductions in both their satisfaction with smoking (p < 0.001) and smoking rate (p < 0.001) from baseline to the end of pre-quit period; participants in the standard patch group did not. The observed reduction of smoking rate was associated with the satisfaction with smoking (p < 0.01), although the mediation effect of satisfaction was small. CONCLUSIONS: Pre-quit treatment caused reductions in satisfaction with smoking and smoking rate. Satisfaction was associated with changes in smoking rate, but the relationship was weak. As such, monitoring reductions in satisfaction do not appear to be a viable method of evaluating responsiveness to treatment.

Efficacy of Varenicline for Cigarette Reduction Before Quitting in Japanese Smokers: A Subpopulation Analysis of the Reduce to Quit Trial.[Pubmed:28365035]

Clin Ther. 2017 Apr;39(4):863-872.

PURPOSE: This prospective analysis of the Japanese subpopulation of the Varenicline reduce to quit study was conducted to evaluate whether results for Japanese participants were consistent with the full study population. METHODS: Patients received Varenicline or placebo for a 24-week treatment period (12-week smoking reduction phase then a 12-week smoking abstinence phase) followed by a 28-week nontreatment, follow-up phase. Participants were to reduce the daily number of cigarettes smoked by at least 50% by week 4 and by a further 50% by week 8, with the goal of achieving complete abstinence by week 12. The primary efficacy end point was the carbon monoxide-confirmed continuous abstinence during weeks 15 to 24. FINDINGS: Overall, 210 Japanese patients were randomly assigned to 1 of the 2 study groups (Varenicline, 107; placebo, 103). Continuous abstinence rates for weeks 15 to 24 were higher for participants in the Varenicline group versus the placebo group (46.7% vs 12.6%; odds ratio = 14.68; 95% CI, 5.38-40.05), and the 7-day point prevalence of abstinence rates were higher for Varenicline versus placebo at week 12 (odds ratio = 13.76; 95% CI, 5.28-35.86). The number of participants with a >/=50% reduction in the number of daily cigarettes smoked from baseline to week 4 and a >/=75% reduction by week 8 was greater in the Varenicline group versus the placebo group (week 4: 59.8% vs 30.1%; week 8: 38.3% vs 12.6%). Serious adverse events were reported in 3.7% of Varenicline participants and 1.0% of placebo participants. IMPLICATIONS: The efficacy and tolerability results of this analysis are consistent with those of the full Varenicline reduce to quit study. Varenicline treatment and cigarette reduction before quitting may provide an alternative approach to smoking cessation in Japanese smokers who are not ready to quit immediately. ClinicalTrials.gov identifier: NCT01370356.

Effects of varenicline on alcohol self-administration and craving in drinkers with depressive symptoms.[Pubmed:28351203]

J Psychopharmacol. 2017 Jul;31(7):906-914.

Varenicline (VAR) is approved to aid in smoking cessation and has been shown to be effective for reducing alcohol consumption in heavy drinkers. Little is known, however, about treatment moderators that may influence efficacy. The current study reanalyzed data from a human laboratory study (Verplaetse et al., 2016) to determine whether VAR was more effective at reducing alcohol use among drinkers reporting symptoms of depression. Participants were 60 adults meeting DSM-IV criteria for alcohol use disorders ( n = 60) who were randomly assigned to receive VAR (1 mg/day, 2 mg/day) or placebo. Following 7 days of medication pretreatment, participants attended a laboratory testing session. They provided self-reported ratings of alcohol craving and performed an ad libitum alcohol consumption task after receiving a priming dose of alcohol (target blood alcohol concentration = 0.030 g/dL). Higher blood VAR plasma levels were associated with less alcohol craving and less drinking among participants with more depressive symptoms. Among participants with fewer depressive symptoms, VAR was associated with more drinking during the ad libitum drinking task. These findings show that depression symptoms may be a moderator of VAR efficacy in alcohol users and provides evidence for the role of nAChRs in depression and alcohol use.

The data set describing cognitive performance after varenicline administration in a 3-choice serial reaction time task in rats.[Pubmed:28337467]

Data Brief. 2017 Mar 3;11:507-509.

The data shows attentional function, impulsivity, motivation, motor function, and motor activity in rats treated with Varenicline, a stop-smoking aid. The data also shows these parameters in rats treated with Varenicline after acute/chronic nicotine administration. Our interpretation and discussion of these data were described in the article "Varenicline Provokes Impulsive Action by Stimulating alpha4beta2 Nicotinic Acetylcholine Receptors in the Infralimbic Cortex in a Nicotine Exposure Status-Dependent Manner" (Ohmura et al., 2017) [1].

Varenicline (CP 526555) is a potent partial agonist for α4β2 nicotinic acetylcholine receptor (nAChR) with an EC50 value of 2.3 μM. Varenicline is a full agonist for α3β4 and α7 nAChRs with EC50 values of 55 μM and 18 μM, respectively. Varenicline is a nicotinic ligand based on the structure of cytisine, has the potential for smoking cessation treatment.

Varenicline,249296-44-4,CP 526555; Champix; Chantix,Natural Products,Nicotinic Receptor, buy Varenicline , Varenicline supplier , purchase Varenicline , Varenicline cost , Varenicline manufacturer , order Varenicline , high purity Varenicline