Cytisine for nicotine addiction treatment: a review of pharmacology, therapeutics and an update of clinical trial evidence for smoking cessation

Abstract

AimsTo review cytisine's history of use, pre‐clinical evidence, clinical pharmacokinetics, efficacy, adverse reactions (ARs) and safety for smoking cessation.MethodsA synoptic review of the use of cytisine as a smoking cessation medication, mechanism of action, pharmacokinetics and safety. Relevant literature on data included in these sections were identified through a search of 11 databases with additional literature obtained from reports and monographs. Three databases (PubMed, EMBASE and www.elibrary.ru) were systematically searched for studies published from 2012 to August 2018 in any language to provide an updated meta‐analysis of cytisine's efficacy and ARs for smoking cessation compared with placebo. We pooled the relative risks (RR) of abstinence in the efficacy analysis and RR of ARs, either reported by the authors or calculated from the reports.ResultsCytisine has been in use since 1964 and is currently marketed in 18 countries. Systemic bioavailability from oral ingestion is high and clearance is primarily renal, with minimal or no metabolism. Brain uptake in animal models is moderate. The plasma half‐life averages 4.8 hours. Eight studies were included for meta‐analysis of efficacy. With heterogeneous results, the overall RR versus placebo of successful continuous abstinence at the longest follow‐up was 1.74 [95% confidence interval (CI) = 1.38–2.19]. Nausea, vomiting, dyspepsia, upper abdominal pain and dry mouth that were mild or moderate were the most common ARs, with RR versus placebo 1.10 (95% CI = 0.95–1.28). The cost of cytisine in eastern and central Europe is several‐fold less than that of other smoking cessation medications.ConclusionsCytisine is a low‐cost medication found to increase the likelihood of smoking cessation. The most frequently reported ARs of cytisine involve gastrointestinal symptoms that are mostly reported as either mild or moderate in severity.

Pyridine alkaloids with activity in the central nervous system

“… 84 , 85 , 86 , 87 , 88 , 89 American Indians are known to have consumed the seeds of L. anagyroides (also known as Cytisus laburnum ) for their purgative and emetic effects during rituals; traditional European medicine used alcoholic extracts of Cytisus plants for constipation, migraine and insomnia; the leaves of L. anagyroides were used as tobacco substitute during World War II. 84 , 85 , 86 , 87 , 88 , 89 In several phytochemical studies examining the biological active secondary metabolite of L. anagyroides , 90 , 91 the aqueous extract of the seeds was found to contain cytisine ( Fig. 11 ), a quinolizidone alkaloid fused to a bispidine ring with absolute configuration later assigned as 1 R ,5 S through stereoselective total synthesis.…”

Stepwise Glucoheptoamidation of Poly(Amidoamine) Dendrimer G3 to Tune Physicochemical Properties of the Potential Drug Carrier: In Vitro Tests for Cytisine Conjugates

“…We hypothesized that partial glucoheptoamidation may reduce amine group toxicity, retaining cationic character of a carrier. Thus, we have chosen the compromised G3 16gh and G3 11gh and attached additionally cytisine because of its low toxicity and common usage in medicine as antismoking drug [21,35]. Our preliminary studies indicated that cytisine was nontoxic not only against normal human fibroblasts (BJ) but also against human squamous cell carcinoma (SCC-15) and U-118 human glioma cells up to 500 µM after 24 h incubation (data not shown).…”

Determination of Cytisine and N-Methylcytisine from Selected Plant Extracts by High-Performance Liquid Chromatography and Comparison of Their Cytotoxic Activity

“…However, the peripheral effects of cytisine (e.g., on the cardiovascular system) are weaker than those of nicotine. Its effectiveness, demonstrated safety, and low price make cytisine a natural alternative to other medicines for smoking cessation [1,2]. This alkaloid is also able to cross the blood-brain barrier.…”

“…Alkaloids are nitrogen-containing organic compounds found in many plants, rarely animals, microorganisms, and fungi. Cytisine (1, [(1R,5S)-1,2,3,4,5,6-hexahydro-1,5-methano-8H-pyrido(1,2a)(1,5) diazocin-8-one]) and N-methylcytisine ([(−)-1,2,3,4,5,6-hexahydro-3-methyl-1,5-methano-8H-pyrido(1,2-a)(1,5)diazocin-8-one]) are quinolizidine alkaloids exhibiting various biological activity [ 1 ]. Cytisine is an α4β2 nicotinic acetylcholine receptor partial agonist, occurring in a various plants.…”