SEARCH RESULTS FOR: Varenicline

Varenicline

Varenicline: Mechanism and Side Effects Nicotine cessation monotherapy Adjuvant to nicotine replacement or behavioural therapy Varenicline Competitive partial agonist of α4β2 nicotinic receptors in the mesolimbic dopamine system which modulate reward signaling associated with nicotine use (E.g., cigarettes, e-cigarettes, vaping, smokeless tobacco) Activated α4β2 nicotinic receptors on cerebral blood vessels causes vasodilation Activation of gastrointestinal α4β2 nicotinic receptors Excessive vasodilation ↑ intracranial pressure Authors: Trevor Low Aliaksandr Savin Reviewers: Andrew Wu Luiza Radu Emily J. Doucette Joel Tappay* *MD at time of publication Headache Varenicline binds central α4β2 nicotinic acetylcholine receptors with higher affinity than exogenous nicotine ↓ Binding of exogenous nicotine to α4β2 nicotinic receptors Ventral tegmental area of midbrain releases ↓ dopamine Nucleus accumbens of ventral striatum receives ↓ dopaminergic signaling ↓ Sensations of pleasure or euphoria with nicotine use ↓ Satisfaction from nicotine consumption ↓ Positive reinforcement with nicotine use Legend: Selective activation of α4β2 nicotinic acetylcholine receptors Partial activation of central α4β2 nicotinic receptors Partial but sustained release of dopamine from ventral tegmental area at a level lower than nicotine Sustained partial release prevents phasic dopamine signaling to the nucleus accumbens Tonic dopamine relieves withdrawal symptoms ↓ Cravings & desire to consume nicotine to relieve withdrawal symptoms ↓ Nicotine use (nicotine cessation) Acetylcholine signaling to area postrema (vomiting center) ↑ Basal levels of dopamine disrupts signaling in nuclei responsible for arousal & sleep initiation ↑ Dopaminergic signaling in the limbic system during sleep ↑ Activation of amygdala (emotions) & hippocampus (memories) during sleep ↑ Intracranial pressure activates meningeal nociceptors Nausea & vomiting ↑ Wakefulness Delay in sleep onset Fragmentation of sleep cycles ↑ Activation causes premature or prolonged REM episodes Dopamine activates cholinergic neurons in nuclei responsible for rapid-eye- movement (REM) sleep Insomnia Abnormal, vivid & emotional dreams Pathophysiology Mechanism Pharmacologic effect Adverse effect Published April 22, 2025 on www.thecalgaryguide.com