Non-nicotinic neuropharmacological strategies for nicotine dependence: beyond bupropion

• Published in: Drug Discovery Today Vol. 8; no. 22; pp. 1025 - 1034
• Main Authors: Cryan, John F., Gasparini, Fabrizio, van Heeke, Gino, Markou, Athina
• Format: Book Review Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 15.11.2003; Elsevier Science
• Subjects: addiction; Animals; Biological and medical sciences; Bupropion - therapeutic use; COPD; CRF; D3 receptor; dependence; Disease Models, Animal; Extinction, Psychological - drug effects; Extinction, Psychological - physiology; GABAB; Humans; Medical sciences; mGLUR5; Neuropharmacology; nicotine; Nicotine - administration & dosage; Nicotine - adverse effects; Pharmacology. Drug treatments; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease); Psychology. Psychoanalysis. Psychiatry; Psychopharmacology; Reinforcement Schedule; smoking cessation; Smoking Cessation - methods; Tobacco Use Disorder - drug therapy; Tobacco Use Disorder - etiology; nicotine; Pharmaceutical Science; addiction; mGLUR5; Pharmacology; Drug Discovery; GABAB; D3 receptor; smoking cessation; CRF; dependence; Molecular Medicine; Physiology; COPD; Dopamine; Targeting; Serotonin; Psychotropic; Corticotropin releasing factor; Review; Cannabinoid; Catecholamine; Glutamate; D3 Dopamine receptor; Tobacco; Bupropion; Dependence; GABA; Neurotransmitter; Antidepressant agent; Drug of abuse; Nicotine
• ISSN: 1359-6446; 1878-5832
• DOI: 10.1016/S1359-6446(03)02890-3

Smoking is a major health problem and is propelled, at least in part, by the addictive properties of nicotine. Two types of pharmacological therapies have been approved for smoking cessation by the US Food and Drug Administration. The first therapy consists of nicotine replacement, substituting the nicotine from cigarettes with safer nicotine formulations. The second therapy is bupropion (Zyban®), an atypical antidepressant, whose use has raised much debate as to how a non-nicotine-based agent can aid in smoking cessation. This review focuses on recent advances that could lead to the development of improved novel pharmacological treatments. These strategies focus on altering reward processes in the brain by modulating various neurotransmitter systems: the most promising include dopamine D 3 receptor antagonists, noradrenaline reuptake inhibitors, GABA B receptor agonists, metabotropic glutamate 5 (mGluR5) receptor antagonists, cannabinoid CB1 receptor antagonists, and corticotropin releasing factor (CRF) 1 receptor antagonists. Can you treat nicotine dependence without targeting nicotinic receptors? Recent evidence suggests that there are many neuropharmacological strategies that could provide exciting avenues for the development of novel smoking cessation agents.