Drugs Currently on the Market for the Treatment of Addiction – Preclinical Background


• Bupropion (Zyban). Bupropion is also an antidepressant (Wellbutrin) with actions that facilitate dopamine and norepinephrine neurotransmission but not serotonin neurotransmission, and it has efficacy in smoking cessation treatment. Bupropion attenuates nicotine withdrawal in rats and decreases mecamylamine-precipitated signs of withdrawal. Bupropion also dose-dependently attenuates the spontaneous nicotine abstinence syndrome and reverses nicotine withdrawal effects in contextual fear conditioning paradigms. Perhaps directly relevant to its therapeutic use, bupropion attenuates the elevation in brain stimulation reward thresholds (decreased reward) during nicotine withdrawal and blocks mecamylamine-precipitated conditioned place aversions. It also decreases nicotine self-administration, an effect amplified with repeated administration, but it failed to block the cue-induced reinstatement of responding. • Varenicline (Chantix). Varenicline is an α4β2 nicotinic acetylcholine receptor partial agonist with efficacy in smoking cessation treatment. When combined with nicotine, varenicline decreases dopamine release in the nucleus accumbens in vivo by itself and has less efficacy than nicotine in stimulating dopamine release. Varenicline partially generalizes to nicotine in drug discrimination studies, consistent with its partial agonist mechanism of action (for further reading, see Koob et al., 2009).

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