Cytisine
[CAS# 485-35-8]

Identification

• Classification: Biochemical >> Plant extracts
• Name: Cytisine
• Synonyms: (1R,5S)-1,2,3,4,5,6-Hexahydro-1,5-methanopyrido[1,2-a][1,5]diazocin-8-one
• Molecular Formula: C₁₁H₁₄N₂O
• Molecular Weight: 190.24
• CAS Registry Number: 485-35-8
• EC Number: 207-616-0
• SMILES: C1[C@H]2CNC[C@@H]1C3=CC=CC(=O)N3C2

Properties

• Density: 1.2±0.1 g/cm³ Calc.^*
• Melting point: 154 - 156 °C (Expl.)
• Boiling point: 413.0±34.0 °C 760 mmHg (Calc.)^*, 482.5 °C (Expl.)
• Flash point: 203.6±25.7 °C (Calc.)^*
• Solubility: water: 100 mM (Expl.)
• Index of refraction: 1.623 (Calc.)^*

^* Calculated using Advanced Chemistry Development (ACD/Labs) Software.

Safety Data

• Hazard Symbols: GHS06;GHS07 Danger
• Risk Statements: H301-H315-H319-H335
• Safety Statements: P261-P264-P264+P265-P270-P271-P280-P301+P316-P302+P352-P304+P340-P305+P351+P338-P319-P321-P330-P332+P317-P337+P317-P362+P364-P403+P233-P405-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Acute toxicity	Acute Tox.	3	H301
Skin irritation	Skin Irrit.	2	H315
Eye irritation	Eye Irrit.	2	H319
Specific target organ toxicity - single exposure	STOT SE	3	H335
Acute toxicity	Acute Tox.	3	H311
Acute toxicity	Acute Tox.	2	H330
Acute toxicity	Acute Tox.	3	H331

• Transport Information: UN 2811

Discovery and Applications

Cytisine is a naturally occurring alkaloid primarily found in plants of the Cytisus genus, including Cytisus laburnum and Laburnum anagyroides. It belongs to the class of quinolizidine alkaloids and is structurally characterized by a tetracyclic skeleton containing a nitrogen atom, which is responsible for its bioactivity. Cytisine has been historically used in traditional medicine and has gained attention in modern pharmacology for its effects on the central nervous system and potential applications in smoking cessation.

The discovery of cytisine dates back to the late 19th century, when it was first isolated from the seeds of the laburnum tree. Early chemical investigations elucidated its structure and alkaloid properties, enabling further study of its pharmacological activities. Researchers recognized that cytisine’s structural similarity to nicotine allows it to interact with nicotinic acetylcholine receptors, which are critical for neurotransmission and reward pathways in the brain.

Pharmacologically, cytisine functions as a partial agonist at nicotinic acetylcholine receptors, particularly the α4β2 subtype, which mediates the addictive effects of nicotine. By binding to these receptors, cytisine can reduce withdrawal symptoms and cravings associated with nicotine dependence while minimizing the euphoric effects of nicotine itself. This mechanism underpins its use as a smoking cessation aid, providing an alternative to nicotine replacement therapies and other pharmacological interventions.

In addition to its role in smoking cessation, cytisine has been investigated for potential neuroprotective and cognitive effects. Some studies suggest that it may modulate neurotransmitter release, improve synaptic plasticity, and exert anti-inflammatory and antioxidant effects in neuronal tissues. These properties indicate potential applications in neurological disorders, although clinical evidence is still limited.

Cytisine exhibits favorable pharmacokinetics for oral administration, including relatively rapid absorption and distribution in the central nervous system. Its half-life supports intermittent dosing, which is practical for therapeutic use in smoking cessation programs. The safety profile of cytisine has been well documented, with most adverse effects being mild and transient, such as nausea, sleep disturbances, or gastrointestinal discomfort.

Clinically, cytisine has been used for decades in Eastern Europe as a prescribed smoking cessation aid. Recent studies and trials have expanded its recognition in other regions, demonstrating its efficacy in promoting sustained abstinence from smoking. Its affordability, natural origin, and pharmacological profile make it a valuable option in public health strategies for reducing tobacco use.

Overall, cytisine is a bioactive quinolizidine alkaloid with significant pharmacological relevance, particularly as a partial agonist of nicotinic acetylcholine receptors. Its applications in smoking cessation, combined with emerging research on neuroprotective and cognitive effects, underscore its potential as a therapeutic agent. Continued studies are needed to further elucidate its mechanisms, optimize dosing strategies, and explore additional clinical applications.

References

2021. Synthesis of N-Arylcytisine Derivatives Using the Copper-Catalyzed Chan-Lam Coupling. Journal of Natural Products, 84(7).
DOI: 10.1021/acs.jnatprod.1c00275

2024. New Hybrid Cytisine Derivatives Containing a Thienopyrimidine Fragment. Chemistry of Natural Compounds, 60(1).
DOI: 10.1007/s10600-024-04266-x

2003. Quinolizidine Alkaloid Profiles of Two Taxa of Teline maderensis. Zeitschrift fur Naturforschung. C, Journal of biosciences, 58(11-12).
DOI: 10.1515/znc-2003-11-1203