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BMJ Open May 2021To evaluate the real-world association between varenicline and neuropsychiatric adverse events (NPAEs) in general and chronic obstructive pulmonary disease (COPD)...
OBJECTIVES
To evaluate the real-world association between varenicline and neuropsychiatric adverse events (NPAEs) in general and chronic obstructive pulmonary disease (COPD) population with and without psychiatric disorders compared with nicotine replacement therapy (NRT) to strengthen the knowledge of varenicline safety.
DESIGN
A retrospective cohort study.
SETTING
Prescription database IADB.nl, the Netherlands.
PARTICIPANTS
New users of varenicline or NRT among general (≥18 years) and COPD (≥40 years) population. Psychiatric subcohort was defined as people prescribed psychotropic medications (≥2) within 6 months before the index date.
OUTCOME MEASURES
The incidence of NPAEs including depression, anxiety and insomnia, defined by new or naive prescriptions of related medications in IADB.nl within 24 weeks after the first treatment initiation of varenicline or NRT.
RESULTS
For the general population in non-psychiatric cohort, the incidence of total NPAEs in varenicline (4480) and NRT (1970) groups was 10.5% and 12.6%, respectively (adjusted OR (aOR) 0.85, 95% CI 0.72 to 1.00). For the general population in psychiatric cohort, the incidence of total NPAEs was much higher, 75.3% and 78.5% for varenicline (1427) and NRT (1200) groups, respectively (aOR 0.82, 95% CI 0.68 to 0.99). For the COPD population (1598), there were no differences in the incidence of NPAEs between comparison groups in both the psychiatric cohort (aOR 0.97, 95% CI 0.66 to 1.44) and non-psychiatric cohort (aOR 0.81, 95% CI 0.54 to 1.20). Results from subgroup or sensitivity analyses also did not reveal increased risks of NPAEs but showed decreased risk of some subgroup NPAEs associated with varenicline.
CONCLUSIONS
In contrast to the concerns of a possible increased risk of NPAEs among varenicline users, we found a relative decreased risk of total NPAEs in varenicline users of the general population in psychiatric or non-psychiatric cohorts compared with NRT and no difference for NPAEs between varenicline and NRT users in smaller population with COPD.
Topics: Benzazepines; Bupropion; Cohort Studies; Humans; Netherlands; Nicotinic Agonists; Pulmonary Disease, Chronic Obstructive; Quinoxalines; Retrospective Studies; Smoking Cessation; Tobacco Use Cessation Devices; Varenicline
PubMed: 34035088
DOI: 10.1136/bmjopen-2020-042417 -
The Cochrane Database of Systematic... Apr 2020Whilst the pharmacological profiles and mechanisms of antidepressants are varied, there are common reasons why they might help people to stop smoking tobacco. Firstly,... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Whilst the pharmacological profiles and mechanisms of antidepressants are varied, there are common reasons why they might help people to stop smoking tobacco. Firstly, nicotine withdrawal may produce depressive symptoms and antidepressants may relieve these. Additionally, some antidepressants may have a specific effect on neural pathways or receptors that underlie nicotine addiction.
OBJECTIVES
To assess the evidence for the efficacy, safety and tolerability of medications with antidepressant properties in assisting long-term tobacco smoking cessation in people who smoke cigarettes.
SEARCH METHODS
We searched the Cochrane Tobacco Addiction Specialized Register, which includes reports of trials indexed in the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, and PsycINFO, clinicaltrials.gov, the ICTRP, and other reviews and meeting abstracts, in May 2019.
SELECTION CRITERIA
We included randomized controlled trials (RCTs) that recruited smokers, and compared antidepressant medications with placebo or no treatment, an alternative pharmacotherapy, or the same medication used in a different way. We excluded trials with less than six months follow-up from efficacy analyses. We included trials with any follow-up length in safety analyses.
DATA COLLECTION AND ANALYSIS
We extracted data and assessed risk of bias using standard Cochrane methods. We also used GRADE to assess the certainty of the evidence. The primary outcome measure was smoking cessation after at least six months follow-up, expressed as a risk ratio (RR) and 95% confidence intervals (CIs). We used the most rigorous definition of abstinence available in each trial, and biochemically validated rates if available. Where appropriate, we performed meta-analysis using a fixed-effect model. Similarly, we presented incidence of safety and tolerance outcomes, including adverse events (AEs), serious adverse events (SAEs), psychiatric AEs, seizures, overdoses, suicide attempts, death by suicide, all-cause mortality, and trial dropout due to drug, as RRs (95% CIs).
MAIN RESULTS
We included 115 studies (33 new to this update) in this review; most recruited adult participants from the community or from smoking cessation clinics. We judged 28 of the studies to be at high risk of bias; however, restricting analyses only to studies at low or unclear risk did not change clinical interpretation of the results. There was high-certainty evidence that bupropion increased long-term smoking cessation rates (RR 1.64, 95% CI 1.52 to 1.77; I = 15%; 45 studies, 17,866 participants). There was insufficient evidence to establish whether participants taking bupropion were more likely to report SAEs compared to those taking placebo. Results were imprecise and CIs encompassed no difference (RR 1.16, 95% CI 0.90 to 1.48; I = 0%; 21 studies, 10,625 participants; moderate-certainty evidence, downgraded one level due to imprecision). We found high-certainty evidence that use of bupropion resulted in more trial dropouts due to adverse events of the drug than placebo (RR 1.37, 95% CI 1.21 to 1.56; I = 19%; 25 studies, 12,340 participants). Participants randomized to bupropion were also more likely to report psychiatric AEs compared with those randomized to placebo (RR 1.25, 95% CI 1.15 to 1.37; I = 15%; 6 studies, 4439 participants). We also looked at the safety and efficacy of bupropion when combined with other non-antidepressant smoking cessation therapies. There was insufficient evidence to establish whether combination bupropion and nicotine replacement therapy (NRT) resulted in superior quit rates to NRT alone (RR 1.19, 95% CI 0.94 to 1.51; I = 52%; 12 studies, 3487 participants), or whether combination bupropion and varenicline resulted in superior quit rates to varenicline alone (RR 1.21, 95% CI 0.95 to 1.55; I = 15%; 3 studies, 1057 participants). We judged the certainty of evidence to be low and moderate, respectively; in both cases due to imprecision, and also due to inconsistency in the former. Safety data were sparse for these comparisons, making it difficult to draw clear conclusions. A meta-analysis of six studies provided evidence that bupropion resulted in inferior smoking cessation rates to varenicline (RR 0.71, 95% CI 0.64 to 0.79; I = 0%; 6 studies, 6286 participants), whilst there was no evidence of a difference in efficacy between bupropion and NRT (RR 0.99, 95% CI 0.91 to 1.09; I = 18%; 10 studies, 8230 participants). We also found some evidence that nortriptyline aided smoking cessation when compared with placebo (RR 2.03, 95% CI 1.48 to 2.78; I = 16%; 6 studies, 975 participants), whilst there was insufficient evidence to determine whether bupropion or nortriptyline were more effective when compared with one another (RR 1.30 (favouring bupropion), 95% CI 0.93 to 1.82; I = 0%; 3 studies, 417 participants). There was no evidence that any of the other antidepressants tested (including St John's Wort, selective serotonin reuptake inhibitors (SSRIs), monoamine oxidase inhibitors (MAOIs)) had a beneficial effect on smoking cessation. Findings were sparse and inconsistent as to whether antidepressants, primarily bupropion and nortriptyline, had a particular benefit for people with current or previous depression.
AUTHORS' CONCLUSIONS
There is high-certainty evidence that bupropion can aid long-term smoking cessation. However, bupropion also increases the number of adverse events, including psychiatric AEs, and there is high-certainty evidence that people taking bupropion are more likely to discontinue treatment compared with placebo. However, there is no clear evidence to suggest whether people taking bupropion experience more or fewer SAEs than those taking placebo (moderate certainty). Nortriptyline also appears to have a beneficial effect on smoking quit rates relative to placebo. Evidence suggests that bupropion may be as successful as NRT and nortriptyline in helping people to quit smoking, but that it is less effective than varenicline. There is insufficient evidence to determine whether the other antidepressants tested, such as SSRIs, aid smoking cessation, and when looking at safety and tolerance outcomes, in most cases, paucity of data made it difficult to draw conclusions. Due to the high-certainty evidence, further studies investigating the efficacy of bupropion versus placebo are unlikely to change our interpretation of the effect, providing no clear justification for pursuing bupropion for smoking cessation over front-line smoking cessation aids already available. However, it is important that where studies of antidepressants for smoking cessation are carried out they measure and report safety and tolerability clearly.
Topics: Anti-Anxiety Agents; Antidepressive Agents; Bupropion; Humans; Nortriptyline; Randomized Controlled Trials as Topic; Selective Serotonin Reuptake Inhibitors; Smoking; Smoking Cessation; Tobacco Use Cessation Devices; Varenicline
PubMed: 32319681
DOI: 10.1002/14651858.CD000031.pub5 -
Frontiers in Pharmacology 2022This study aimed to build a nasal semi-physiologically based pharmacokinetic (PBPK) model to predict the intranasal pharmacokinetic (PK) of the OC-01(varenicline) nasal...
This study aimed to build a nasal semi-physiologically based pharmacokinetic (PBPK) model to predict the intranasal pharmacokinetic (PK) of the OC-01(varenicline) nasal spray and accelerate the development of this drug. Based on the physiology of the human upper respiratory system, the semi-PBPK model was established and validated using systemic plasma PK data of varenicline previously observed in Americans and Chinese. Drug concentrations, both in respiratory tissue and plasma circulation system, were well simulated, and it was indicated that local concentration at the target site (nasal cavity) was significantly higher than that of plasma when OC-01 nasal spray was administered. The nasal semi-PBPK model successfully depicted the absorption and distribution of intranasal varenicline in the respiratory tissues and provided an alternative to clinical PK study of OC-01 nasal spray in Chinese. Meanwhile the current study presented a viable framework for predicting respiratory concentrations for other novel nasal spray drugs by semi-PBPK modeling.
PubMed: 35873554
DOI: 10.3389/fphar.2022.910629 -
Therapeutic Advances in Respiratory... 2019Smoking causes various diseases and is a major public health threat worldwide. Therefore, promoting smoking cessation is the most important intervention contributing to... (Review)
Review
Smoking causes various diseases and is a major public health threat worldwide. Therefore, promoting smoking cessation is the most important intervention contributing to maintaining the health of smokers and nonsmokers and saving enormous financial expense. We reviewed existing and emerging smoking-cessation pharmacotherapies from the Cochrane Database of Systemic Reviews, PubMed, Ovid, and ClinicalTrials.gov databases. A literature review revealed that bupropion may be appropriate for patients interested in reducing smoking who dislike, or who have failed, nicotine-replacement therapy (NRT). Additionally, varenicline and NRT are efficacious first-line smoking cessation treatments and should be given to all individuals unless contraindicated.
Topics: Bupropion; Cigarette Smoking; Humans; Nicotinic Agonists; Recurrence; Smoking Cessation; Smoking Cessation Agents; Tobacco Use Cessation Devices; Tobacco Use Disorder; Treatment Outcome; Varenicline
PubMed: 31533544
DOI: 10.1177/1753466619875925 -
Jornal Brasileiro de Pneumologia :... 2020This study aimed to investigate acute and chronic effects of varenicline on lung tissue in an experimental study.
OBJECTIVE
This study aimed to investigate acute and chronic effects of varenicline on lung tissue in an experimental study.
METHODS
A total of 34 rats were randomly allocated into study (varenicline) and control groups. The rats were divided into two groups (i) control group, (ii) varenicline group. Then, the rats in the each group were sub-divided equally in turn as acute (C1; V1) and chronic (C2; V2) ; all rats of acute and chronic groups were sacrificed under the anesthesia on the 45th day for acute group [C1 (n=5) and V1 (n=12)] and the 90th day for chronic group [C2 (n=5) and V2 (n=12)], respectively. Thus, biochemical and histopathological analysis were carried out.
RESULTS
Thirty four rats completed the study, 24 were in varenicline group and 10 were in control group. In chronic exposure to varenicline, oxidant levels comprising of malondialdehyde (MDA), and myeloperoxidase (MPO) increased and superoxide dismutase (SOD), catalase (CAT), glutathione (GSH) and glutathione peroxidase (GPx) levels, named as antioxidants, decreased significantly when compared to the control group. MDA and MPO levels were also significantly higher and SOD, CAT, GPx, GSH levels were also significantly lower in chronic varenicline group when compared to acute varenicline group. These findings were also supported by histopathological observations.
CONCLUSION
This is the first study, which evaluated pulmonary effects of varenicline experimentally on an animal model. It was observed that chronic varenicline treatments cause inflammation and lung cell injury.
Topics: Animals; Catalase; Glutathione; Glutathione Peroxidase; Lung; Malondialdehyde; Oxidative Stress; Rats; Superoxide Dismutase; Varenicline
PubMed: 32130342
DOI: 10.36416/1806-3756/e20180406 -
Journal of Psychoactive Drugs 2018Few studies have evaluated treatment for co-occurring cannabis and tobacco use. The objective of this pilot study was to evaluate the feasibility and preliminary... (Comparative Study)
Comparative Study Randomized Controlled Trial
Few studies have evaluated treatment for co-occurring cannabis and tobacco use. The objective of this pilot study was to evaluate the feasibility and preliminary effectiveness of varenicline for co-occurring cannabis and tobacco use. Participants who reported cannabis use on ≥5 days per week were recruited from an urban, outpatient opioid treatment program (OTP). Participants were randomized to either four weeks of standard OTP clinical care (SCC; medication-assisted treatment for opioid use disorder and individual behavioral counseling), followed by four weeks of SCC plus varenicline (SCC+VT), or to four weeks of SCC+VT followed by four weeks of SCC. All participants contributed feasibility and outcome data during both study phases. Of 193 persons screened, seven were enrolled. Retention at eight weeks was 100%. No adverse effects prompted varenicline discontinuation. Participants reported lower cannabis craving during the SCC+VT phase compared to baseline, and lower frequencies and quantities of cannabis use compared to both baseline and the SCC alone phase. In the SCC+VT phase, participants also reported fewer cigarettes per day. Among persons with co-occurring cannabis and tobacco use, varenicline is well-tolerated and may reduce cannabis craving, cannabis use, and tobacco use.
Topics: Adult; Behavior Therapy; Craving; Cross-Over Studies; Feasibility Studies; Female; Humans; Male; Marijuana Abuse; Middle Aged; Pilot Projects; Smoking Cessation Agents; Tobacco Use Disorder; Varenicline
PubMed: 28952897
DOI: 10.1080/02791072.2017.1370746 -
Nicotine & Tobacco Research : Official... Feb 2022Varenicline is the most efficacious drug for smoking cessation; saliva varenicline concentrations can be useful for the evaluation of adherence in smoking cessation...
INTRODUCTION
Varenicline is the most efficacious drug for smoking cessation; saliva varenicline concentrations can be useful for the evaluation of adherence in smoking cessation trials. Saliva is a useful noninvasive matrix for mail-in specimen collection, if stable. We investigated the stability of varenicline in saliva at different storage temperatures simulating the time it takes to mail in a sample.
METHODS
We evaluated the concentrations of varenicline, nicotine, cotinine, 3'-hydroxycotinine, and 3'-hydroxycotinine/cotinine (3HC/COT) ratio in quality control saliva samples (and after repeated freezing and thawing), and in smokers' saliva samples, stored for up to 21 days at room temperature (~25°C), 4°C, and -80°C.
RESULTS
In saliva quality control samples, concentrations of varenicline, nicotine, cotinine, 3'-hydroxycotinine, and 3HC/COT remained unchanged and showed little within-sample variation (CV ≤ 5.5%) for up to 21 days at the three storage temperatures; they were also not altered after three thaw-freeze cycles. In smokers' saliva, a significant main effect of storage duration, but not temperature, was observed for varenicline, cotinine, and 3'-hydroxycotinine, but not for nicotine or the 3HC/COT ratio. However, these changes were within analytical (i.e., equipment) variation resulting in little within-sample variation (CV ≤ 5.8%) for all analytes in smokers' saliva.
CONCLUSIONS
Varenicline, the other analytes, and the 3HC/COT ratio remained stable in saliva during storage for 21 days at all temperatures tested and after repeated freezing and thawing with only minor changes in concentration over time. These findings support the potential use of mail-in approach for saliva samples in varenicline smoking cessation clinical trials.
IMPLICATIONS
Assessing saliva varenicline concentrations can be useful for the evaluation of adherence in smoking cessation trials. Saliva is a noninvasive matrix suitable for mail-in specimen collection. This is the first investigation of stability of varenicline in saliva. Varenicline, nicotine, cotinine, 3'-hydroxycotinine, and 3HC/COT were stable in saliva for up to 21 days at room temperature (~25°C), 4°C, and -80°C, supporting the use of a mail-in approach for saliva specimen in smoking cessation trials.
Topics: Cotinine; Humans; Nicotine; Saliva; Smoking Cessation; Temperature; Varenicline
PubMed: 34460924
DOI: 10.1093/ntr/ntab173 -
Addiction (Abingdon, England) Oct 2022In Australia, patterns of use of smoking cessation medications and factors associated with their dispensing are currently not known. This study aimed to measure the...
BACKGROUND AND AIMS
In Australia, patterns of use of smoking cessation medications and factors associated with their dispensing are currently not known. This study aimed to measure the demographic and clinical factors associated with varenicline dispensing compared with nicotine replacement therapy (NRT) and bupropion among first-time users of Pharmaceutical Benefits Scheme (PBS) subsidised smoking cessation medicines in Australia and to characterise those who discontinued varenicline treatment prematurely.
DESIGN
Retrospective, population-based study. Logistic regression was used to identify factors associated with varenicline dispensing compared with NRT and bupropion. Sensitivity analyses estimated the proportion of individuals who completed the recommended 12 weeks of varenicline treatment.
SETTING AND PARTICIPANTS
First-time users of PBS subsidised smoking cessation medicines in Australia. Individuals first dispensed a smoking cessation medicine between 2011 and 2019 were identified from a 10% random sample of the national dispensing claims data.
MEASUREMENTS
The outcome for the regression analysis was the dispensing of varenicline compared with NRT and bupropion. The dispensing of a smoking cessation medicine was identified using the World Health Organization Anatomical Therapeutic Chemical Classification System and PBS item codes. Independent variables included demographic and clinical characteristics such as sex, age, concessional status, year of treatment initiation and comorbidities identified using the Rx-Risk index. The proportion of people who discontinued varenicline treatment after the initiation pack was determined using prescription refill data.
FINDINGS
A total of 94 532 people had their first PBS subsidised smoking cessation medicine. Of these, 62 367 (66.0%) were dispensed varenicline, 29 949 (31.7%) NRT and 2216 (2.3%) bupropion. The odds of varenicline dispensing were higher in males (OR, 1.18; 95% CI, 1.14-1.21), but lower in older adults (0.86 [0.82-0.90] in above 30 years to 0.49 [0.47-0.52] in 61 years and above), among concession beneficiaries (0.44; 0.43-0.46), and those with congestive heart failure (0.60; 0.53-0.68), depression (0.61; 0.54-0.69), anxiety (0.70; 0.66-0.73), psychotic illness (0.39; 0.37-0.42), and chronic obstructive pulmonary disease (0.87; 0.82-0.92). The majority (37 670; 60.4%) of those dispensed varenicline discontinued treatment after the initiation pack. Anxiety and psychotic illnesses were significantly more prevalent in those who discontinued treatment. Only 2804 (4.5%) of those dispensed varenicline completed 12 weeks of treatment.
CONCLUSION
Individuals dispensed varenicline in Australia appear to be healthier compared with those who are dispensed nicotine replacement therapy or bupropion.
Topics: Aged; Australia; Benzazepines; Bupropion; Humans; Male; Nicotine; Nicotinic Agonists; Quinoxalines; Retrospective Studies; Smoking; Smoking Cessation; Tobacco Use Cessation Devices; Varenicline
PubMed: 35603915
DOI: 10.1111/add.15949 -
The Cochrane Database of Systematic... Aug 2016Smoking cessation is the most important treatment for smokers with chronic obstructive pulmonary disease (COPD), but little is known about the effectiveness of different... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Smoking cessation is the most important treatment for smokers with chronic obstructive pulmonary disease (COPD), but little is known about the effectiveness of different smoking cessation interventions for this particular group of smokers.
OBJECTIVES
To evaluate the effectiveness of behavioural or pharmacological smoking cessation interventions, or both, in smokers with COPD.
SEARCH METHODS
We searched all records in the Cochrane Airways Group Specialised Register of Trials. In addition to this electronic search, we searched clinical trial registries for planned, ongoing, and unpublished trials. We searched all databases from their inception. We checked the reference lists of all included studies and of other systematic reviews in relevant topic areas. We searched for errata or retractions from eligible trials on PubMed. We conducted our most recent search in March 2016.
SELECTION CRITERIA
We included randomised controlled trials assessing the effectiveness of any behavioural or pharmacological treatment, or both, in smokers with COPD reporting at least six months of follow-up abstinence rates.
DATA COLLECTION AND ANALYSIS
Two review authors independently extracted the data and performed the methodological quality assessment for each study. We resolved any disagreements by consensus.
MAIN RESULTS
We included 16 studies (involving 13,123 participants) in this systematic review, two of which were of high quality. These two studies showed that nicotine sublingual tablet and varenicline increased the quit rate over placebo (risk ratio (RR) 2.60 (95% confidence interval (CI) 1.29 to 5.24) and RR 3.34 (95% CI 1.88 to 5.92)). Pooled results of two studies also showed a positive effect of bupropion compared with placebo (RR 2.03 (95% CI 1.26 to 3.28)). When pooling these four studies, we found high-quality evidence for the effectiveness of pharmacotherapy plus high-intensity behavioural treatment compared with placebo plus high-intensity behavioural treatment (RR 2.53 (95% CI 1.83 to 3.50)). Furthermore, we found some evidence that high-intensity behavioural treatment increased abstinence rates when compared with usual care (RR 25.38 (95% CI 8.03 to 80.22)) or low-intensity behavioural treatment (RR 2.18 (95% CI 1.05 to 4.49)). Finally, the results showed effectiveness of various combinations of psychosocial and pharmacological interventions.
AUTHORS' CONCLUSIONS
We found high-quality evidence in a meta-analysis including four (1,540 participants) of the 16 included studies that a combination of behavioural treatment and pharmacotherapy is effective in helping smokers with COPD to quit smoking. Furthermore, we conclude that there is no convincing evidence for preferring any particular form of behavioural or pharmacological treatment.
Topics: Adult; Behavior Therapy; Bupropion; Combined Modality Therapy; Female; Humans; Male; Nicotine; Nicotinic Agonists; Pulmonary Disease, Chronic Obstructive; Randomized Controlled Trials as Topic; Smoking Cessation; Varenicline
PubMed: 27545342
DOI: 10.1002/14651858.CD010744.pub2 -
The Journal of Pharmacology and... Apr 2021Nicotine has previously been shown to augment the antinociceptive effects of -opioid agonists in squirrel monkeys without producing a concomitant increase in behavioral...
Nicotine has previously been shown to augment the antinociceptive effects of -opioid agonists in squirrel monkeys without producing a concomitant increase in behavioral disruption. The present studies were conducted to extend these findings by determining the ability of the nicotinic acetylcholine receptor (nAChR) agonist epibatidine and partial 42 nAChR agonist varenicline to selectively augment the antinociceptive effects of the -opioid receptor (MOR) full agonist fentanyl, the MOR partial agonist nalbuphine, and the -opioid receptor (KOR) agonist U69,593 in male squirrel monkeys. Results indicate that both nAChR ligands selectively increased the antinociceptive effects of nalbuphine and that epibatidine increased the antinociceptive effects of U69,593 without altering effects on operant behavior. However, neither epibatidine nor varenicline enhanced the antinociceptive effects of fentanyl, perhaps due to its high efficacy. The enhancement of nalbuphine's antinociceptive effects by epibatidine, but not varenicline, could be antagonized by either mecamylamine or dihydro--erythroidine, consistent with 42 mediation of epibatidine's effects but suggesting the involvement of non-nAChR mechanisms in the effects of varenicline. The present results support previous findings showing that an nAChR agonist can serve as an adjuvant for MOR antinociception and, based on results with U69,593, further indicate that the adjuvant effects of nAChR drugs may also apply to antinociception produced by KOR. Our findings support the further evaluation of nAChR agonists as adjuvants of opioid pharmacotherapy for pain management and point out the need for further investigation into the mechanisms by which they produce opioid-adjuvant effects. SIGNIFICANCE STATEMENT: Nicotine has been shown to augment the antinociceptive effects of -opioid receptor analgesics without exacerbating their effects on operant performance. The present study demonstrates that the nicotinic acetylcholine receptor (nAChR) agonist epibatidine and partial α4β2 nAChR agonist varenicline can also augment the antinociceptive effects of nalbuphine, as well as those of a -opioid receptor agonist, without concomitantly exacerbating their behaviorally disruptive effects. These findings support the view that nAChR agonists and partial agonists may have potential as adjuvant therapies for opioid-based analgesics.
Topics: Analgesics, Non-Narcotic; Analgesics, Opioid; Animals; Bridged Bicyclo Compounds, Heterocyclic; Conditioning, Operant; Drug Synergism; Fentanyl; Male; Nalbuphine; Nicotinic Agonists; Nociception; Pyridines; Saimiri; Varenicline
PubMed: 33441370
DOI: 10.1124/jpet.120.000423