Chemical formula: C₁₁H₁₄N₂O Molecular mass: 190.242 g/mol PubChem compound: 10235
The use of cytisine allows for a gradual reduction of nicotine dependence by relieving withdrawal symptoms. Cytisine is a plant alkaloid (found, among others, in seeds of golden chain, genus Laburnum), with a chemical structure similar to nicotine. It has an effect on acetylcholine nicotinic receptors. The action of cytisine is similar to that of nicotine, but in general weaker. Cytisine competes with nicotine for the same receptors and gradually displaces nicotine due to its stronger binding. It has lower ability to stimulate nicotinic receptors, mainly α4β2 subtype (it is their partial agonist) and less than nicotine passes into the central nervous system.
It is hypothesized that in the central nervous system cytisine acts on the mechanism involved in nicotine dependence and on the release of neurotransmitters. It prevents nicotine‑dependent full activation of the mesolimbic dopamine system and moderately increases level of dopamine in the brain, what alleviates the central symptoms of nicotine withdrawal. In the peripheral nervous system, cytisine stimulates and then infects the autonomic ganglia of the nervous system, causes a reflex stimulation of breathing and secretion of catecholamines from the core part of the adrenal gland, raises blood pressure and prevents peripheral symptoms of nicotine withdrawal.
After oral administration of labeled cytisine in mice at a dose of 2 mg/kg, 42% of the administered dose was absorbed. The maximum concentration of cytisine in the blood was reported after 120 minutes, and within 24 hours 18% of the dose was excreted in the urine. The half-life of cytisine, determined after intravenous administration, was 200 minutes. Nearly ⅓ of the dose administered intravenously was excreted in the urine in 24 hours and 3% of the dose within 6 hours with faeces. The highest concentrations of drug were obtained in liver, adrenal glands and kidneys. After intravenous administration, the concentration of cytisine in the bile was 200 times higher than in blood. Constant level of cytisine concentration in the blood was accomplished in two phases after its percutaneous administration to the rabbits. The first phase lasted 24 hours and the second phase for the next three days. In the first phase, the rate of absorption and the blood level of the drug were two times higher than in the second phase. The volume of distribution (Vd) in rabbits after oral and intravenous administration was 6.21 l/kg and 1.02 l/kg, respectively. After subcutaneous administration of 1 mg/kg cytisine to male rats, the blood concentration was 516 ng/ml, and the concentration in the brain was 145 ng/ml. The concentration in the brain was less than 30% of the concentration in the blood. In similar experiments with subcutaneously administered nicotine, the concentration of nicotine in the brain was 65% of the concentration in the blood.
The pharmacokinetic properties of cytisine were tested after a single oral dose of the formulation containing 1.5 mg of cytisine in 36 healthy volunteers. After oral administration, cytisine was quickly absorbed from the gastrointestinal tract. The mean maximum plasma concentration of 15.55 ng/ml was achieved after a mean of 0.92 hours.
Cytisine was slightly metabolised.
64% of the dose was excreted unchanged in the urine within 24 hours. The mean half-life in plasma was approx. 4 hours. The mean residence time (MRT) was approx. 6 hours.
There is no data in renally and hepatically impaired patients and the influence of food on the exposure of cytosine is unknown.
Non-clinical data reveal no special hazard for humans based on non-GLP studies of repeat dose toxicity, genotoxicity and toxicity to reproduction and development.
Repeat dose toxicity studies in mice, rats and dogs did not show significant toxicity in relation to haematopoiesis, gastric mucosa, kidneys, liver and other internal organs.
Cytisine was not genotoxic in an in vivo study in mice. There was no evidence of embryotoxicity of cytisinein rats.
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