Tesofensine, a novel triple monoamine reuptake inhibitor, induces appetite suppression by indirect stimulation of α1 adrenoceptor and dopamine D1 receptor pathways in the diet-induced obese rat

Neuropsychopharmacology

Volumn 35, Issue 7, 2010, Pages 1464-1476

  Axel, Anne Marie D ^a   Mikkelsen, Jens D ^b   Hansen, Henrik H ^a  

^a NEUROSEARCH A S   (Denmark)

^b Mental Health Center Glostrup   (Denmark)

Author keywords

1 adrenoceptor; Anti obesity effect; Diet induced obesity; Dopamine D1 receptor; Food intake; Monoamine reuptake inhibitor

Indexed keywords

2 (2 METHOXY 1,4 BENZODIOXAN 2 YL) 2 IMIDAZOLINE; 8 CHLORO 2,3,4,5 TETRAHYDRO 3 METHYL 5 PHENYL 1H 3 BENZAZEPIN 7 OL HYDROGEN MALEATE; ALPHA 1 ADRENERGIC RECEPTOR; DOPAMINE 1 RECEPTOR; DOPAMINE RECEPTOR BLOCKING AGENT; ENZYME INHIBITOR; HALOPERIDOL; NGB 2904; PRAZOSIN; RITANSERIN; TESOFENSINE; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ANIMAL MODEL; APPETITE; ARTICLE; BODY WEIGHT; CONTROLLED STUDY; DIET; DRUG ACTIVITY; DRUG ANTAGONISM; FOOD INTAKE; HYPOPHAGIA; LIPID DIET; MALE; NONHUMAN; NUCLEOTIDE SEQUENCE; OBESITY; PRIORITY JOURNAL; RAT; STIMULATION;

ADRENERGIC ALPHA-ANTAGONISTS; ANIMALS; APPETITE DEPRESSANTS; BENZAZEPINES; BICYCLO COMPOUNDS, HETEROCYCLIC; BODY WEIGHT; DIET; DISEASE MODELS, ANIMAL; DOPAMINE ANTAGONISTS; DOSE-RESPONSE RELATIONSHIP, DRUG; DRUG INTERACTIONS; EATING; FEEDING BEHAVIOR; MALE; OBESITY; PRAZOSIN; RATS; RATS, SPRAGUE-DAWLEY; RECEPTORS, ADRENERGIC, ALPHA-1; RECEPTORS, DOPAMINE D1; SIGNAL TRANSDUCTION; TIME FACTORS;

EID: 77952426181     PISSN: 0893133X     EISSN: None     Source Type: Journal    
DOI: 10.1038/npp.2010.16     Document Type: Article

References (56)

1. Alberto CO, Trask RB, Quinlan ME, Hirasawa M (2006). Bidirectional dopaminergic modulation of excitatory synaptic transmission in orexin neurons. J Neurosci 26: 10043-10050.
2. Astrup A, Madsbad S, Breum L, Jensen TJ, Kroustrup JP, Larsen TM (2008a). Effect of tesofensine on bodyweight loss, body composition, and quality of life in obese patients: a randomised, double-blind, placebo-controlled trial. Lancet 372: 1906-1913.
3. Astrup A, Meier DH, Mikkelsen BO, Villumsen JS, Larsen TM (2008b). Weight loss produced by tesofensine in patients with Parkinsons or Alzheimers disease. Obesity (Silver Spring) 16: 1363-1369.
4. Balcioglu A, Wurtman RJ (2000). Sibutramine, a serotonin uptake inhibitor, increases dopamine concentrations in rat striatal and hypothalamic extracellular fluid. Neuropharmacology 39: 2352-2359.
5. Billes SK, Cowley MA (2007). Inhibition of dopamine and norepinephrine reuptake produces additive effects on energy balance in lean and obese mice. Neuropsychopharmacology 32: 822-834.
6. Billes SK, Cowley MA (2008). Catecholamine reuptake inhibition causes weight loss by increasing locomotor activity and thermogenesis. Neuropsychopharmacology 33: 1287-1297.
7. Bina KG, Cincotta AH (2000). Dopaminergic agonists normalize elevated hypothalamic neuropeptide Y and corticotropin-releas-ing hormone, body weight gain, and hyperglycemia in ob/ob mice. Neuroendocrinology 71: 68-78.
8. Bray GA (2000). A concise review on the therapeutics of obesity. Nutrition 16: 953-960.
9. Clifton PG, Kennett GA (2006). Monoamine receptors in the regulation of feeding behaviour and energy balance. CNS Neurol Disord Drug Targets 5: 293-312.
10. Connoley IP, Liu YL, Frost I, Reckless IP, Heal DJ, Stock MJ (1999). Thermogenic effects of sibutramine and its metabolites. Br J Pharmacol 126: 1487-1495.
11. Davis LM, Michaelides M, Cheskin LJ, Moran TH, Aja S, Watkins PA et al (2008). Bromocriptine administration reduces hyper-phagia and adiposity and differentially affects Dopamine D2 receptor and transporter binding in leptin-receptor-deficient zucker rats and rats with diet-induced obesity. Neuroendocrinology 89: 152-162.
12. Deupree JD, Burke WJ, Bylund DB (2008). Alpha-2 adrenergic-induced changes in rectal temperature in adult and 13-day old rats following acute and repeated desipramine administration. BMC Pharmacol 8: 17.
13. Durcan MJ, McWilliam JR, Campbell IC, Neale MC, Dunn G (1988). Chronic antidepressant drug regimes and food and water intake in rats. Pharmacol Biochem Behav 30: 299-302.
14. Fetissov SO, Meguid MM, Sato T, Zhang LH (2002). Expression of dopaminergic receptors in the hypothalamus of lean and obese Zucker rats and food intake. Am J Physiol Regul Integr Comp Physiol 283: R905-R910.
15. Gardier AM, Trouvin JH, Orosco M, Nicolaidis S, Jacquot C (1989). Effects of food intake and body weight on a serotonergic turnover index in rat hypothalamus. Brain Res Bull 22: 531-535.
16. Gehlert DR, Dreshfield L, Tinsley F, Benvenga MJ, Gleason S, Fuller RW et al (1998). The selective norepinephrine reuptake inhibitor, LY368975, reduces food consumption in animal models of feeding. J Pharmacol Exp Ther 287: 122-127.
17. Geiger BM, Behr GG, Frank LE, Caldera-Siu AD, Beinfeld MC, Kokkotou EG et al (2008). Evidence for defective mesolimbic dopamine exocytosis in obesity-prone rats. FASEB J 22: 2740-2746.
18. Glick SD, Haskew RE, Maisonneuve IM, Carlson JN, Jerussi TP (2000). Enantioselective behavioral effects of sibutramine metabolites. Eur J Pharmacol 397: 93-102.
19. Golozoubova V, Strauss F, Malmlof K (2006). Locomotion is the major determinant of sibutramine-induced increase in energy expenditure. Pharmacol Biochem Behav 83: 517-527.
20. Grignaschi G, Fanelli E, Scagnol I, Samanin R (1999). Studies on the role of serotonin receptor subtypes in the effect of sibutramine in various feeding paradigms in rats. Br J Pharmacol 127: 1190-1194.
21. Halford JC, Harrold JA, Boyland EJ, Lawton CL, Blundell JE (2007). Serotonergic drugs: effects on appetite expression and use for the treatment of obesity. Drugs 67: 27-55.
22. Heal DJ, Cheetham SC, Prow MR, Martin KF, Buckett WR (1998). A comparison of the effects on central 5-HT function of sibutramine hydrochloride and other weight-modifying agents. Br J Pharmacol 125: 301-308.
23. Jackson HC, Bearham MC, Hutchins LJ, Mazurkiewicz SE, Needham AM, Heal DJ (1997). Investigation of the mechanisms underlying the hypophagic effects of the 5-HT and noradrena-line reuptake inhibitor, sibutramine, in the rat. Br J Pharmacol 121: 1613-1618.
24. Kraszewski KZ, Cincotta AH (2000). Increased responsiveness of ventromedial hypothalamic neurons to norepinephrine in obese versus lean mice: relation to the metabolic syndrome. Int J Mol Med 5: 349-355.
25. Kung MP, Choi SR, Hou C, Zhuang ZP, Foulon C, Kung HF (2004). Selective binding of 2-[125I]iodo-nisoxetine to norepinephrine transporters in the brain. Nucl Med Biol 31: 533-541.
26. Kuo DY (2002). Co-administration of dopamine D1 and D2 agonists additively decreases daily food intake, body weight and hypothalamic neuropeptide Y level in rats. J Biomed Sci 9: 126-132.
27. Lehr T, Staab A, Tillmann C, Nielsen EO, Trommeshauser D, Schaefer HG et al (2008). Contribution of the active metabolite M1 to the pharmacological activity of tesofensine in vivo: a pharmacokinetic-pharmacodynamic modelling approach. Br J Pharmacol 153: 164-174.
28. Levin BE, Keesey RE (1998). Defense of differing body weight set points in diet-induced obese and resistant rats. Am J Physiol 274: R412-R419.
29. Liu YL, Connoley IP, Heal DJ, Stock MJ (2004). Pharmacological characterisation of the thermogenic effect of bupropion. Eur J Pharmacol 498: 219-225.
30. McQuade JA, Benoit SC, Woods SC, Seeley RJ (2003). 7-OH-DPAT selectively reduces intake of both chow and high fat diets in different food intake regimens. Pharmacol Biochem Behav 76: 517-523.
31. McQuade JA, Benoit SC, Xu M, Woods SC, Seeley RJ (2004). High-fat diet induced adiposity in mice with targeted disruption of the dopamine-3 receptor gene. Behav Brain Res 151: 313-319.
32. Meguid MM, Fetissov SO, Blaha V, Yang ZJ (2000a). Dopamine and serotonin VMN release is related to feeding status in obese and lean Zucker rats. Neuroreport 11: 2069-2072.
33. Meguid MM, Fetissov SO, Varma M, Sato T, Zhang L, Laviano A et al (2000b). Hypothalamic dopamine and serotonin in the regulation of food intake. Nutrition 16: 843-857.
34. Meguid MM, Yang ZJ, Laviano A (1997). Meal size and number: relationship to dopamine levels in the ventromedial hypotha-lamic nucleus. Am J Physiol 272: R1925-R1930.
35. Mori RC, Guimaraes RB, Nascimento CM, Ribeiro EB (1999). Lateral hypothalamic serotonergic responsiveness to food intake in rat obesity as measured by microdialysis. Can J Physiol Pharmacol 77: 286-292.
36. Morien A, McMahon L, Wellman PJ (1993). Effects on food and water intake of the alpha 1-adrenoceptor agonists amidephrine and SK&F-89748. Life Sci 53: 169-174.
37. Morien A, Wellman PJ, Fojt J (1995). Diurnal rhythms of paraventricular hypothalamic norepinephrine and food intake in rats. Pharmacol Biochem Behav 52: 169-174.
38. Nelson DL, Gehlert DR (2006). Central nervous system biogenic amine targets for control of appetite and energy expenditure. Endocrine 29: 49-60.
39. Orosco M, Nicolaidis S (1992). Spontaneous feeding-related monoaminergic changes in the rostromedial hypothalamus revealed by microdialysis. Physiol Behav 52: 1015-1019.
40. Orosco M, Rouch C, Meile MJ, Nicolaidis S (1995). Spontaneous feeding-related monoamine changes in rostromedial hypothala-mus of the obese Zucker rat: a microdialysis study. Physiol Behav 57: 1103-1106.
41. Pfeffer AO, Samson HH (1988). Haloperidol and apomorphine effects on ethanol reinforcement in free feeding rats. Pharmacol Biochem Behav 29: 343-350.
42. Pothos EN, Sulzer D, Hoebel BG (1998). Plasticity of quantal size in ventral midbrain dopamine neurons: possible implications for the neurochemistry of feeding and reward. Appetite 31: 405.
43. Racotta R, Soto-Mora LM (1993). Specificity of alpha-and beta-adrenergic inhibition of water and food intake. Physiol Behav 53: 361-365.
44. Rittenhouse PA, Bakkum EA, Levy AD, Li Q, Carnes M, van de Kar LD (1994). Evidence that ACTH secretion is regulated by serotonin2A/2C (5-HT2A/2C) receptors. J Pharmacol Exp Ther 271: 1647-1655.
45. Scislowski PW, Tozzo E, Zhang Y, Phaneuf S, Prevelige R, Cincotta AH (1999). Biochemical mechanisms responsible for the attenuation of diabetic and obese conditions in ob/ob mice treated with dopaminergic agonists. Int J Obes Relat Metab Disord 23: 425-431.
46. Shimizu H, Fisler S, Bray GA (1994). Extracellular hypothalamic monoamines measured by in vivo microdialysis in a rat model of dietary fat-induced obesity. Obes Res 2: 100-109.
47. Spiller K, Xi ZX, Peng XQ, Newman AH, Ashby Jr CR, Heidbreder C et al (2008). The selective dopamine D3 receptor antagonists SB-277011A and NGB 2904 and the putative partial D3 receptor agonist BP-897 attenuate methamphetamine-enhanced brain stimulation reward in rats. Psychopharmacology (Berl) 196: 533-542.
48. Stanley BG, Schwartz DH, Hernandez L, Hoebel BG, Leibowitz SF (1989). Patterns of extracellular norepinephrine in the paraven-tricular hypothalamus: relationship to circadian rhythm and deprivation-induced eating behavior. Life Sci 45: 275-282. (Pubitemid 19196595)
49. Volkow ND, Wise RA (2005). How can drug addiction help us understand obesity? Nat Neurosci 8: 555-560.
50. Wellman PJ (2000). Norepinephrine and the control of food intake. Nutrition 16: 837-842.
51. Wellman PJ (2005). Modulation of eating by central catecholamine systems. Curr Drug Targets 6: 191-199.
52. Wellman PJ, Davies BT (1992). Reversal of cirazoline-and phenylpropanolamine-induced anorexia by the alpha 1-receptor antagonist prazosin. Pharmacol Biochem Behav 42: 97-100.
53. Wilmot CA, Sullivan AC, Levin BE (1988). Effects of diet and obesity on brain alpha 1-and alpha 2-noradrenergic receptors in the rat. Brain Res 453: 157-166.
54. Wortley KE, Hughes ZA, Heal DJ, Stanford SC (1999). Comparison of changes in the extracellular concentration of noradrenaline in rat frontal cortex induced by sibutramine or d-amphetamine: modulation by alpha2-adrenoceptors. Br J Pharmacol 127: 1860-1866.
55. Yang ZJ, Meguid MM, Chai JK, Chen C, Oler A (1997). Bilateral hypothalamic dopamine infusion in male Zucker rat suppresses feeding due to reduced meal size. Pharmacol Biochem Behav 58: 631-635.
56. Young 3rd WS, Kuhar MJ (1980). Noradrenergic alpha 1 and alpha 2 receptors: light microscopic autoradiographic localization. Proc Natl Acad Sci USA 77: 1696-1700.