Nicotine Receptor Agonists

Nicotine is the chemical in tobacco that results in addiction to smoking and other forms of nicotine consumption.  Nicotine stimulates the release of dopamine in the brain, which is associated with pleasurable effects of smoking including relaxation and release of tension. Nicotine also results in the release of epinephrine, which increases heart rate and blood pressure.  Withdrawal from nicotine causes anxiety, headaches, and difficulty concentrating, which is one of the reasons that stopping smoking is so challenging.  Bupropion and varenicline are two drugs that are used to assist with smoking cessation. Bupropion lowers the seizure threshold and varenicline can result in vivid dreams, hallucinations, and suicidal ideations.  

Class Drugs

• Nicotine

Class Mechanism of Action

Dose Dependent Action

• Nicotinic receptor stimulation depolarizes autonomic ganglia

• First results in stimulation, then leads to paralysis at high doses by ganglionic blockade

Addictive Effects

Increases release of the following hormones:

• Dopamine: Increases pleasure, acts as appetite suppressant

• Norepinephrine: Alertness, appetite suppression

• Acetylcholine: Alertness

• Glutamine: Memory enhancement

• Serotonin: Increases mood

• Beta-endorphin: Decreases anxiety

• GABA: Decreases anxiety

Class Adverse Effects

At high doses:

• CNS: Medullary paralysis results in central respiratory paralysis and hypotension

• PNS: GI and bladder motility stop, and hypotension occurs due to ganglionic block

General Side-Effects

• Tremor

• Irritability

• Diarrhea: parasympathetic stimulation increases GI motility

• Increased blood pressure: stimulation of adrenal medulla and sympathetic ganglia

• Increased heart rate: stimulation of adrenal medulla and sympathetic ganglia

Withdrawal Syndrome

• Irritability

• Anxiety

• Difficulty concentrating

• Headaches

Smoking Cessation

• Patch, gum, inhaler, lozenge, or nasal spray used to reduce cravings

• Bupropion (antidepressant) used to reduce cravings (seizure risk)

• Varenicline

Drug Table

Drug Name	Application	Comments	Image
Nicotine			"Cigarette"
Varenicline	Smoking cessation; Decreases the euphoria and other rewarding effects of nicotine	Partial nicotinic receptor agonist in CNS; Adverse Effects:Nightmares	"Incline Bench"