Rimonabant

Rimonabant

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  rimonabant By drsalman kareem 1st yr resident Department of psychiatry
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  rimonabant • Anorecticanti obesity drug • Inverse agonist of cannabinoid receptor • first selective CB1 receptor blocker. • Main effect in the reduction of appetite • Started in july 2006 • Suspended in 16 Jan 2009 by EMEA
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  Endocannabinoid system (ECS):Overview Gelfand EV, Cannon CP. J Am Coll Cardiol. 2006;47:1919-26. Pagotto U et al. Ann Med. 2005;37:270-5. Endocannabinoid ligands • Produced on demand • Act locally • Inactivated rapidly • Bind to transmembrane G-protein receptors, principally inhibiting neurotransmitter release Cannabinoid receptor type 1 (CB1) Cannabinoid receptor type 2 (CB2) Cannabinoid receptor type 1 (CB1) Most widespread CB receptor Immune cells (brain, spinal cord; peripheral nervous system, organs, tissues)
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  Implications of CB1receptor activation Central nervous system Peripheral tissue Appetite Motivation to eat/smoke Liver GI tract Skeletal muscle Lipogenesis Adipose tissue Altered glucose metabolism Gelfand EV, Cannon CP. J Am Coll Cardiol. 2006;47:1919-26. Pagotto U et al. Ann Med. 2005;37:270-5. Hypothalamus Limbic system
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  uses • Smokingcessation – found to be effective in assisting some members to quit smoking. Studies with Rimonabant and Tobacco Use (STRATUS) done in 6000 subjects shows it aods in smoking and prevents weight gain in former smokers. COCHRAne review – mayincrease the odds of quitting approximately 1n half folds.
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  • Addiction -reduced resumption of cocaine-seeking responses. – also reduce ethanol- and opiate-seeking behavior. • Blockage of cannabis effects - Rimonabant blocks the psychoactiveand some of the cardiovascular effects of Δ9-tetrahydrocannabinol (THC) in humans. • Reverse marijuana
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  • Memory -hypothesised that rimonabant may improve short-term memory. • Effect on physical activity • Effect on male fertility
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  Side effects •Depression • Nausea • Anxiety • Suicidal Tendency • Unpredictable mood swings • Insomnia
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  • CB(1) receptorsare widely distributed in the central nervous system and are involved in the modulation of emotion, stress and habituation responses, behaviours that are thought to be dysregulated in human psychiatric disorders. • CB(1) receptor activation may, in some cases, precipitate episodes of psychosis and panic, while its inhibition may lead to behaviours reminiscent of depression and anxiety-related disorders
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  Study published inLANCET • Rimonabant patient has 2.5 times risk discontinuinf for depression • 3.5 times discontinuing due to anxiety.