Taranabant: Cannabinoid CB1 inverse agonist antiobesity drug

Drugs of the Future

Volumn 33, Issue 3, 2008, Pages 206-212

  Cole, P ^a   Serradell, N ^a   Rosa, E ^a   Bolos J ^a  

^a PROUS SCIENCE   (Spain)

Author keywords

[No Author keywords available]

Indexed keywords

4 (1,1 DIMETHYLHEPTYL) 1',2',3',4',5',6' HEXAHYDRO 2,3' DIHYDROXY 6' (3 HYDROXYPROPYL)BIPHENYL; ETHINYLESTRADIOL PLUS NORGESTIMATE; MK 9470; PLACEBO; RIMONABANT; SIBUTRAMINE; TARANABANT; TRACER; UNCLASSIFIED DRUG;

ANXIETY DISORDER; AREA UNDER THE CURVE; CLINICAL TRIAL; COMBINATION CHEMOTHERAPY; CONTROLLED CLINICAL TRIAL; DEPRESSION; DRUG ACTIVITY; DRUG ANTAGONISM; DRUG BINDING; DRUG BLOOD LEVEL; DRUG INHIBITION; DRUG SAFETY; DRUG STRUCTURE; DRUG SYNTHESIS; DRUG WITHDRAWAL; ENERGY EXPENDITURE; FOOD INTAKE; GASTROINTESTINAL SYMPTOM; HEADACHE; HUMAN; IRRITABILITY; MAXIMUM PLASMA CONCENTRATION; NAUSEA; NONHUMAN; OBESITY; RANDOMIZED CONTROLLED TRIAL; REVIEW; SIDE EFFECT; SINGLE DRUG DOSE; WEIGHT GAIN; WEIGHT REDUCTION;

EID: 42449124076     PISSN: 03778282     EISSN: None     Source Type: Journal    
DOI: 10.1358/dof.2008.033.03.1185054     Document Type: Review

References (43)

1. Hagmann, W.K., Lin, L.S., Shah, S.K. et al. (Merck & Co., Inc.). Substituted amides. CA 2478183, EP 1496838, JP 2005519958, JP 2006257090, US 2004058820, US 6972295, WO 03077847.
2. Hagmann, W.K., Lin, L.S., Shah, S.K. et al. (Merck & Co., Inc.). Substituted amides active at the cannabinoid-1 receptor. WO 2004048317.
3. Lin, L.S., Lanza, T.J. Jr., Jewell, J.P. et al. Discovery of N-[(1S,2S)-3-(4-chlorophenyl)-2-(3-cyanophenyl)-1-methylpropyl] -2-methyl-2-[[5-(trifluoromethyl)pyridin-2-yl]oxy]propanamide (MK-0364), a novel, acyclic cannabinoid-1 receptor inverse agonist for the treatment of obesity. J Med Chem 2006, 49(26): 7584-7.
4. Chen, C., Frey, L.F., Shultz, S. et al. Catalytic, enantioselective synthesis of taranabant, a novel, acyclic cannabinoid-1 receptor inverse agonist for the treatment of obesity. Org Proc Res Devel 2007, 11(3): 616-23.
5. Campos, K.R., Klapars, A., McWilliams, J.C. et al. (Merck & Co., Inc.). Formation of tetra-substituted enamides and stereo-selective reduction thereof. WO 2006017045.
6. Weissman, S.A. (Merck & Co., Inc.). Cyanation of aromatic halides. US 2006106223.
7. Smyth, S., Heron, A. Diabetes and obesity: The twin epidemics. Nat Med 2006, 12(1): 75-80.
8. Ogden, C.L. et al. Prevalence of overweight and obesity in the United States, 1999-2004. JAMA - J Am Med Assoc 2006, 295(13): 1549-55.
9. Allison, D.B. et al. Annual deaths attributable to obesity in the United States. JAMA - J Am Med Assoc 1999, 282(16): 1530-8.
10. Poirier, P. et al. Obesity and cardiovascular disease: Pathophysiology, evaluation, and effect of weight loss: An update of the 1997 American Heart Association Scientific Statement on Obesity and Heart Disease from the Obesity Committee of the Council on Nutrition, Physical Activity, and Metabolism. Circulation 2006, 113(6): 898-918.
11. U.S. Department of Health and Human Services. The Surgeon General's call to action to prevent and decrease overweight and obesity. U.S. Department of Health and Human Services, Public Health Service, Office of the Surgeon General, 2001.
12. Bray, G.A., Greenway, F.L. Pharmacological treatment of the overweight patient. Pharmacol Rev 2007, 59(2): 151-84.
13. Breivogel, C.S., Childers, S.R. The functional neuroanatomy of brain cannabinoid receptors. Neurobiol Dis 1998, 5(6, Pt. B): 417-31.
14. Berthoud, H.R. Multiple neural systems controlling food intake and body weight. Neurosci Biobehav Rev 2002, 26(4): 393-428.
15. Seeley, R.J., Woods, S.C. Monitoring of stored and available fuel by the CNS: Implications for obesity. Nat Rev Neurosci 2003, 4(11): 901-9.
16. Schwartz, M.W., Porte, D. Jr. Diabetes, obesity, and the brain. Science 2005, 307(5708): 375-9.
17. Greenberg, I. Kuehnle, J., Mendelson, J.H., Bernstein, J.G. Effects of marihuana use on body weight and caloric intake in humans. Psychopharmacology 1976, 49(1): 79-84.
18. Gardner, E.L., Vorel, S.R. Cannabinoid transmission and reward-related events. Neurobiol Dis 1998, 5(6): 502-33.
19. Arnone, M., Maruani, J., Chaperon, F., Thiébot, M-H., Poncelet, M., Soubrié, P., Le Fur, G. Selective inhibition of sucrose and ethanol intake by SR 141716, an antagonist of central cannabinoid (CB1) receptors. Psychopharmacology 1997, 132(1): 104-6.
20. Simiand, J., Keane, M., Keane, P.E., Soubrie, P. SR141716, a CB1 cannabinoid receptor antagonist, selectively reduces sweet food intake in marmoset. Behav Pharmacol 1998, 9(2): 179-81.
21. Freedland, C.S., Poston, J.S., Porrino, L.J. Effects of SR141716A, a central cannabinoid receptor antagonist, on food-maintained responding. Pharmacol Biochem Behav 2000, 67(2): 265-70.
22. Di Marzo, V., Goparaju, S.K., Wang, L. et al. Leptin-regulated endocannabinoids are involved in maintaining food intake. Nature 2001, 10(6830): 822-5.
23. Blundell, J.E., Jebb, S.A., Stiubbs, R.J. et al. Effect of rimonabant on energy intake, motivation to eat and body weight with or without hypocaloric diet: The REBA study. Obesity Rev 2006, 7(Suppl. 2): 104.
24. Liu, Y.L., Connoley, I.P., Wilson, C.A., Stock, M.J. Effects of the cannabinoid CB1 receptor antagonist SR141716 on oxygen consumption and soleus muscle glucose uptake in Lep(ob)/Lep(ob) mice. Int J Obesity 2005, 29(2): 183-7.
25. Ravinet Trillou, C., Delgorge, C., Menet, C., Arnone, C., Soubrié, P. CB1 cannabinoid receptor knockout in mice leads to leanness, resistance to diet-induced obesity and enhanced leptin sensitivity. Int J Obes Relat Metab Disord 2004, 28(4): 640-8.
26. Christensen, R., Kristensen, P.K., Bartels, E.M., Bliddal, H., Astrup, A. Efficacy and safety of the weight-loss drug rimonabant: A meta-analysis of randomised trials. Lancet 2007, 370(9600): 1671-2.
27. Fong, T.M., Guan, X.M., Marsh, D.J. et al. Antiobesity efficacy of a novel cannabinoid-1 receptor inverse agonist, N-[(1S,2S)-3-(4-chlorophenyl)-2- (3-cyanophenyl)-1-methylpropyl]-2-methyl-2-[[5-(trifluoromethyl)pyridin-2-yl] oxy]propanamide (MK-0364), in rodents. J Pharmacol Exp Ther 2007, 321(3): 1013-22.
28. Stribling, D.S., Camacho, R.C., Lin, L.S. et al. In vivo characterization of a novel and selective cannabinoid receptor 1 inverse agonist. 36th Annu Meet Soc Neurosci (Oct 14-18, Atlanta) 2006, Abst 457.9/CC1.
29. Yu, H., Stribling, D.S., Shearman, L.P. et al. A novel cannabinoid 1 receptor inverse agonist reduces food intake and body weight in rats - Correlation of pharmacological effect with brain receptor occupancy. 36th Annu Meet Soc Neurosci (Oct 14-18, Atlanta) 2006, Abst 457.10/CC2.
30. Addy, C., Wright, H., Van Laere, K. et al. The acyclic CB1R inverse agonist taranabant mediates weight loss by increasing energy expenditure and decreasing caloric intake. Cell Metab 2008, 7(1): 68-78.
31. De Lepeleire, I., Addy, C., Rothenberg, P. et al. Brain CB-1 receptor occupancy of taranabant in lean subjects using CB-1R PET. 43rd Annu Meet Eur Assoc Study Diabetes (EASD) (Sept 17-21, Amsterdam) 2007, Abst 0831.
32. Addy, C., Rothenberg, P., Burns, D. et al. Clinical evaluation of brain CB-1 receptor occupancy of a novel CB-1R inverse agonist using CB-1R PET. 67th Annu Meet Sci Sess Am Diabetes Assoc (ADA) (June 22-26, Chicago) 2007, Abst 2738-PO.
33. Addy, C., Heymsfield, S., Cilissen, C. et al. Taranabant increases energy expenditure in overweight and moderately obese subjects. 43rd Annu Meet Eur Assoc Study Diabetes (EASD) (Sept 17-21, Amsterdam) 2007, Abst 0832.
34. Addy, C., Heymsfield, S., Cilissen, C. et al. MK-0364, a novel cannabinoid-1 receptor inverse agonist, increases energy expenditure in overweight and moderately obese subjects. 67th Annu Meet Sci Sess Am Diabetes Assoc (ADA) (June 22-26, Chicago) 2007, Abst 1828-P.
35. Wright, D., Stevens, C., Cilissen, C. et al. The CB-1R inverse agonist taranabant reduces acute food intake in overweight/obese male volunteers. 43rd Annu Meet Eur Assoc Study Diabetes (EASD) (Sept 17-21, Amsterdam) 2007, Abst 0833.
36. Stevens, C., Cilissen, C., De Smet, M. et al. MK-0364, a CB-1R inverse agonist, reduces acute food intake in overweight/obese male volunteers. 67th Annu Meet Sci Sess Am Diabetes Assoc (ADA) (June 22-26, Chicago) 2007, Abst 1830-P.
37. A study of MK0364 in obese patients (NCT00131391). ClinicalTrials.gov Web site, February 14, 2008.
38. An eighteen month efficacy and safety study in obese patients (NCT00131430). ClinicalTrials.gov Web site, February 14, 2008.
39. A one year investigational drug study to assess weight loss in patients with type 2 diabetes mellitus (NCT00430742). ClinicalTrials.gov Web site, February 14, 2008.
40. A weight maintenance study in obese patients (NCT00420589). ClinicalTrials.gov Web site, February 14, 2008.
41. An investigational drug study in obese (considerably overweight) patients (NCT00109148). ClinicalTrials.gov Web site, February 15, 2008.
42. A study to investigate a research drug as an aid for smoking cessation in chronic cigarette smokers (NCT00109135). ClinicalTrials.gov Web site, February 15, 2008.
43. Schwartz, J.L., Yuan, J., Li, S. et al. Influence of taranabant, a novel cannabinoid-1 receptor (CB-1R) inverse agonist, on ethinyl estradiol and norelgestromin pharmacokinetics. 36th Annu Meet Am Coll Clin Pharmacol (ACCP) (Sept 9-11, San Francisco) 2007, Abst 43.