Table 2: Central mechanisms of action of anti-obesity pharmacotherapies.

Central Subsystem Drugs targets Possible receptor subtypes involved Monoamine system (indirect agonists and subtype selective receptor antagonists) Single therapies (i) Dex/fenfluramine (WD), fluoxetine (i) 5HT (ii) Phentermine/Diethylpropion (ST) (ii) DA, NA (iii) Sibutramine (iii) α 1, β 1, β 3 adrenergic and 5HT2B/C (iv) Bupropion (iv) DA, NA (v) Tesofensine (v) DA, NA, 5HT (vi) Lorcaserin (vi) 5HT2C Opioid system (μ-opioid receptor antagonist) (i) Naltrexone (i) μ-opioid (ii) Topiramate (ii) AMPA/kainite glutamate* (iii) Zonisamide (iii) 5HT, DA∗ Cannabinoid system Single therapies: (i) Rimonabant (WD) (i) CB1 (ii) Taranabant (DC) (ii) CB1 Monoamine/Opioid system Bupropion/naltrexone (i) DA, NA/μ-opioid Bupropion/zonisamide (ii) DA, NA/5HT, DA∗ Neuropeptide Y/Agouti-related peptide system Pramlintide/metreleptin (i) Calcitonin receptor∗/Leptin receptor

5HT: serotonergic, DA: dopaminergic, NA: noradrenergic, WD:withdrawn; DC: phase III trials discontinued; ST: short term;∗: unknown; AMPA: α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate.