Varenicline is a partial agonist of the nicotinic acetylcholine receptor (nAChR) subtype alpha4beta2. Nicotine stimulation of central alpha4beta2 nAChRs located at presynaptic terminals in the nucleus accumbens causes the release of the neurotransmitter dopamine, which may be associated with the experience of pleasure; nicotine addiction constitutes a physiologic dependence related to this dopaminergic reward system. As an AChR partial agonist, varenicline attenuates the craving and withdrawal symptoms that occur with abstinence from nicotine but is not habit-forming itself.
Varenicline is a prescription medication used to treat nicotine addiction. It both reduces cravings for and decreases the pleasurable effects of cigarettes and other tobacco products. Varenicline is a prescription medication used to treat smoking addiction. This medication is the first approved nicotinic receptor partial agonist. Specifically, varenicline is a partial agonist of the alpha4/beta2 subtype of the nicotinic acetylcholine receptor.
It is a high-affinity partial agonist for the α4β2 nicotinic acetylcholine receptor subtype (nACH) that leads to the release of dopamine in the nucleus accumbens when activated, and therefore, has the capacity to reduce the feelings of craving and withdrawal caused by smoking cessation. In this respect, it is similar to cytisine and different from the nicotinic antagonist bupropion and nicotine replacement therapies (NRTs) like nicotine patches and nicotine gum.
Mechanism of action of Varenicline
Varenicline is an alpha-4 beta-2 neuronal nicotinic acetylcholine receptor, partial agonist. The drug shows high selectiviyty for this receptor subclass, relative to other nicotinic receptors (>500-fold alpha-3 beta-4, >3500-fold alpha-7, >20,000-fold alpha-1 beta gamma delta) or non-nicotinic receptors and transporters (>2000-fold). The drug competitively inhibits the ability of nicotine to bind to and activate the alpha-4 beta-2 receptor. The drug exerts mild agonistic activity at this site, though at a level much lower than nicotine; it is presumed that this activation eases withdrawal symptoms.
Varenicline is a selective alpha4beta2 nicotinic acetylcholine receptor, partial agonist. The drug binds with high affinity and selectivity to alpha4beta2 nicotinic acetylcholine receptors located in the brain and stimulates receptor-mediated activity, but at a substantially lower level than nicotine;1 6 this low-level receptor stimulation and subsequent moderate, sustained release of mesolimbic dopamine are thought to reduce craving and withdrawal symptoms associated with smoking cessation. Varenicline also blocks the ability of nicotine to activate alpha4beta2 receptors, preventing nicotine-induced stimulation of the mesolimbic dopaminergic system and thereby reducing the reinforcement and reward effects of cigarette smoking.
Indications of Varenicline
- Varenicline is used as an adjunct in the cessation of cigarette smoking.
- For use as an aid in smoking cessation.
- Smoking Cessation.
Contra-Indications of Varenicline
- Having Thoughts of Suicide
- alcohol intoxication
- Heart attack
- Acute Syndrome of the Heart
- Transient Ischemic Attack
- Peripheral Vascular Disease
- severe renal impairment
- Feel Like Throwing Up
- Increased Cardiovascular Event Risk
Dosage of Varenicline
Strengths: 0.5 mg; 1 mg; 0.5 mg-1 mg
- Smoking Cessation.
- Days 1 to 3: 0.5 mg orally once a day
- Days 4 to 7: 0.5 mg orally twice a day
- Days 8 to end of treatment: 1 mg orally twice a day
Side Effects of Varenicline
The most common
- Abnormal dreams
- bloated or full feeling
- change in taste
- difficulty having a bowel movement (stool)
- dry mouth
- excess air or gas in the stomach or intestines
- the general feeling of discomfort or illness
- stomach pain or cramping
- a headache
- stomach pain;
- back pain, joint or muscle pain.
- problems with your vision (including color vision);
- sudden chest pain or trouble breathing;
- pain or swelling in one or both legs;
- a migraine headache;
- pale skin, feeling light-headed or short of breath, rapid heart rate, trouble concentrating; or
- Abdominal or stomach pain, discomfort, or tenderness
- chills or fever
- difficulty with moving
- a headache, severe and throbbing
- joint or back pain
- muscle aching or cramping
- muscle pains or stiffness
- chest pressure or squeezing pain in the chest
- discomfort in arms, shoulders, neck or upper back
- excessive sweating
- feeling of heaviness, pain, warmth and/or swelling in a leg or in the pelvis
- sudden tingling or coldness in an arm or leg
- sudden slow or difficult speech
- sudden drowsiness or need to sleep
- fast breathing
- sharp pain when taking a deep breath
- fast or slow heartbeat
- coughing up blood
- rust colored urine
- decreased amount of urine
- change in vision
- chest pain or tightness
- a cough
- arm, back, or jaw pain
- blurred vision
- chest pain or discomfort
- extra heartbeats
- a headache
- mood or mental changes
- muscle pain or cramps
- muscle spasm or jerking of all extremities
Drug Interactions of Varenicline
Varenicline may interact with the following drugs, supplements & may change the efficacy of the drugs
- H2-antagonists (e.g., cimetidine, famotidine, ranitidine)
- nicotine replacement therapy
- quinolone antibiotics (e.g., ciprofloxacin, levofloxacin, norfloxacin)
FDA Pregnancy Category C
This medication should not be used during pregnancy unless the benefits outweigh the risks. If you become pregnant while taking this medication, contact your doctor immediately.
It is not known if varenicline passes into breast milk. If you are a breastfeeding mother and are taking this medication, it may affect your baby. Talk to your doctor about whether you should continue breastfeeding. The safety and effectiveness of this medication have not been established for children.