Centrally acting drugs target receptors in neural pathways controlling appetite and may also increase peripheral energy expenditure. However, because these receptors are often present in areas of the brain unrelated to food intake, behavioral specificity is difficult to attain.

Centrally acting drugs that are prescribed for weight loss include benzphetamine, buproprion, phentermine, rimonabant, sertraline, sibutramine and topimarate.

• BENZPHETAMINE

  Tradename(s)	Didrex
  Company(ies)	Pfizer (Pharmacia & Upjohn Company)
  Available doses	50 mg
  Dose per day	once daily
  Side-effects	agitation and insomnia
  Elimination half-life
  Metabolism
  US patent status	generic
  US FDA status	Approved October 1960
  EMEA status
  Indication
  Didrex Tablets are indicated in the management of exogenous obesity as a short term adjunct (a few weeks) in a regimen of weight reduction based on caloric restriction.
  Comments
  Benzphetamine is metabolized by the human body into amphetamine and methamphetamine metabolites.

• BUPROPRION

  Tradename(s)	Wellbutrin XL® and Zyban®
  Company(ies)	GlaxoSmithKline
  Available doses	150 mg and 300 mg
  Dose per day	once daily
  Side-effects	agitation and insomnia
  Elimination half-life	20 hours
  Metabolism	extensively metabolized
  US patent status	generic
  US FDA status	off-label use - not approved for weight loss
  EMEA status
  Indication
  Wellbutrin® was approved by the US FDA in December of 1985 in 150 mg and 300 mg tabletsisfor the treatment of major depressive disorder. Zyban® formulation was approved by the US FDA in May 1997 as an aid to smoking cessation treatment and is only available in 150 mg tablets.
  Comments
  Bupropion inhibits neuronal uptake of norepinephrine and dopamine. Bupropion is not approved for weight-loss, however it is prescribed for off-label use for weight management.

• PHENTERMINE

  Tradename(s)	Adipex®
  Company(ies)	Gate Pharmaceuticals and others
  Available doses	30 mg
  Dose per day	once daily
  Side-effects	cardiovascular and central nervous system effects
  Elimination half-life	20 hours
  Metabolism
  US patent status	generic
  US FDA status	approved
  EMEA status	approved
  Indication
  Phentermine is indicated as a short-term adjunct in a regimen of weight reduction based on exercise, behavioral modification and caloric restriction in the management of exogenous obeisty for patients with an initial body mass index ≥ 30 kg/m2 or > 27 kg/m2 in the presence of other risk factor(s), such as type 2 diabetes or dyslipidaemia.
  Comments
  Phentermine stimulates the central nervous system and elevates blood pressure.

• RIMONABANT

  Tradename(s)	Acomplia® / Zimulti®
  Company(ies)	Sanofi-Aventis
  Available doses	20 mg
  Dose per day	once daily
  Side-effects	depressive disorder and anxiety
  Elimination half-life	16 days
  Metabolism	metabolized by CYP3A and amidohydrolase
  US patent status	2014
  US FDA status	not approved due to safety concerns
  EMEA status	Approved June 2006 - Sales suspended in October 2008
  Indication
  In Europe, rimonabant is indicated as an adjunct to diet and exercise for the treatment of obese patients (BMI ≥ 30 kg/m2), or overweight patients (BMI > 27 kg/m2) with associated risk factor(s), such as type 2 diabetes or dyslipidaemia.
  Comments
  Rimonabant is a cannabinoid (CB-1) receptor antagonist US FDA did not approve rimonabant (Zimulti) primarily due to concerns about psychiatric side effects such as anxiety and depression Sanofi-Aventis reported sales of €31M in 2006 and €79M in 2007 Sanofi-Aventis is presently seeking to reposition this product as therapy for type2 diabetes and is working towards a submission of a type 2 diabetes indication in 2009 Acomplia sales were suspended in the European Union in October 2008. According to the EMEA, obese and overweight people using Acomplia have twice the risk of mental disorders than those taking a placebo. On November 5, 2008, Sanofi-Aventis suspended furhter clinical development of rimonabant.

• SERTRALINE

  Tradename(s)	Zoloft®
  Company(ies)	Pfizer
  Available doses	25 mg, 50 mg and 100 mg
  Dose per day	once daily
  Side-effects	weight loss
  Elimination half-life	26 hours
  Metabolism	extensively metabolized
  US patent status	generic
  US FDA status	off-label use - not approved for weight loss
  EMEA status
  Indication
  Zoloft® was approved in December 1991 by the US FDA for the treatment of major depressive disorder in adults.
  Comments
  Sertraline inhibits serotonin uptake. Sertraline is not approved for weight-loss, however it is prescribed for off-label use for weight management.

• SIBUTRAMINE

  Tradename(s)	Meridia® and Reductil®
  Company(ies)	Abbott Laboratories
  Available doses	5 mg, 10 mg and 15 mg
  Dose per day	once daily
  Side-effects	increase in blood pressure
  Elimination half-life	17.2 hours
  Metabolism	metabolized in the liver principally by the cytochrome P450 (3A4) isoenzyme
  US patent status
  US FDA status	approved November 1997
  EMEA status
  Indication
  Sibutramine is indicated for the management of obesity, including weight loss and maintenance of weight loss, and should be used in conjunction with a reduced calorie diet. Sibutramine is recommended for obese patients with an initial body mass index ≥ 30 kg/m2, or ≥ 27 kg/m2 in the presence of other risk factors (e.g., diabetes, dyslipidemia, controlled hypertension).
  Comments
  Sibutramine effects norepinephrine, serotonin and dopamine reuptake inhibition.

• TOPIMARATE

  Tradename(s)	Topamax®
  Company(ies)	Ortho McNeil Pharma
  Available doses	25 mg, 50 mg, 100 mg and 200 mg
  Dose per day	once daily
  Side-effects	paresthesia (tingling)
  Elimination half-life	21 hours
  Metabolism	eliminated unchanged in the urine
  US patent status	2009
  US FDA status	off-label use - not approved for weight loss
  EMEA status
  Indication
  Topamax was approved in December 1991 by the US FDA as initial monotherapy in patients 10 years of age and older with partial onset or primary generalized tonic-clonic seizures and for adults for the prophylaxis of migraine headache.
  Comments
  Topiramate blocks sodium channels, augments neurotransmitter gamma-aminobutyrate at some subtypes of the GABA-A receptor.