Lack of protection with a novel, selective melanocortin receptor subtype-4 agonist RY767 in a rat transient middle cerebral artery occlusion stroke model

Pharmacology

Volumn 83, Issue 1, 2008, Pages 38-44

  Regan, Christopher ^a   Shepherd, Cherrie ^a   Strack, Alison ^a   Weinberg, David ^a   Nargund, Ravi ^a   Ye, Zhixiong ^a   Pollard, Patrick ^a   Fong, Tung ^a   Reynolds, Ian ^a   Lynch, Joseph ^a  

^a MERCK RESEARCH LABORATORIES   (United States)

Author keywords

Cerebral infarct; Cerebral ischemia; Melanocortin; Neuroprotection; Stroke

Indexed keywords

DIZOCILPINE; MELANOCORTIN 4 RECEPTOR; MELANOCORTIN RECEPTOR AGONIST; N [1 [2 [4 [[1 TERT BUTYL 3 (2,4 DIFLUOROPHENYL)PIPERIDIN 4 YL]CARBONYL]PIPERAZIN 1 YL] 4 CHLORO 5 METHYLPHENYL]ETHYL] N ISOPROPYLACETAMIDE BISPHOSPHATE; RY 767; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; BRAIN INFARCTION SIZE; BRAIN ISCHEMIA; CONTROLLED STUDY; DRUG EFFECT; DRUG EFFICACY; MALE; MIDDLE CEREBRAL ARTERY OCCLUSION; NEUROPROTECTION; NONHUMAN; PRIORITY JOURNAL; RAT; STROKE;

ADMINISTRATION, ORAL; ANIMALS; CHO CELLS; CRICETINAE; CRICETULUS; DISEASE MODELS, ANIMAL; DIZOCILPINE MALEATE; HUMANS; INFARCTION, MIDDLE CEREBRAL ARTERY; INJECTIONS, INTRAVENOUS; MALE; NEUROPROTECTIVE AGENTS; PIPERAZINES; PIPERIDINES; RATS; RATS, WISTAR; RECEPTOR, MELANOCORTIN, TYPE 4; REPERFUSION INJURY;

EID: 57049153444     PISSN: 00317012     EISSN: None     Source Type: Journal    
DOI: 10.1159/000178811     Document Type: Article

References (30)

1. Dirnagl U, Iadecola C, Moskowitz MA: Pathobiology of ischemic stroke: an integrated view. Trends Neurosci 1999;22:391-397.
2. Wang X: Investigational anti-inflammatory agents for the treatment of ischaemic brain injury. Expert Opin Investig Drugs 2005;14:393-409.
3. Huh SK, Lipton JM, Batjer HH: The protective effects of alpha-melanocyte stimulating hormone on canine brain stem ischemia. Neurosurgery 1997;40:132-139.
4. Huang Q, Tatro JB: α-Melanocyte stimulating hormone suppresses intracerebral tumor necrosis factor-α and interleukin-1b expression following transient cerebral ischemia in mice. Neurosci Lett 2002;334:186-190.
5. 7] α-melanocyte-stimulating hormone for long-lasting protection against ischemic stroke, in Mongolian gerbils. Eur J Pharmacol 2006;538:48-56.
6. Giuliani D, Mioni C, Altavilla D, Leone S, Bazzani C, Minutoli L, Bitto A, Cainazzo MM, Marini H, Zaffe D, Botticelli AR, Pizzali R, Savio M, Necchi D, Schioth HB, Bertolini A, Squadrito F, Guarini S: Both early and delayed treatment with melanocortin 4 receptor-stimulating melanocortins produced neuroprotection in cerebral ischemia. Endocrinology 2006;147:1126-1135.
7. Giuliani D, Ottani A, Mioni C, Bazzani C, Galantucci M, Minutoli L, Bitto A, Zaffe D, Botticelli AR, Squadrito F, Guarini S: Neuroprotection in focal cerebral ischemia owing to delayed treatment with melanocortins. Eur J Pharmacol 2007;570:57-65.
8. Ujjainwalla F, Sebhat IK: Small molecule ligands of the human melanocortin-4 receptor. Curr Top Med Chem 2007;7:1068-1084.
9. Bednarek MA, Silva MV, Arison B, MacNeil T, Kalyani RN, Huang RR, Weinberg DH: Structure-function studies on the cyclic peptide MT-II, lactam derivative of α-melanotropin. Peptides 1999;20:401-409.
10. Longa EZ, Weinstein PR, Carlson S, Cummins R: Reversible middle cerebral artery occlusion without craniectomy in rats. Stroke 1989;20:84-91.
11. Regan HK, Detwiler TJ, Huang JC, Lynch JJ, Regan CP: An improved automated method to quantitate infarct volume in triphenyltetrazolium stained rat brain sections. J Pharmacol Toxicol Methods 2007;56:339-342.
12. Wikberg JES, Muceniece R, Mandrika I, Prusis P, Lindblom J, Post C, Skottner A: New aspects on the melanocortins and their receptors. Pharmacol Res 2000;42:393-420.
13. Catania A, Gatti S, Colombo G, Lipton JM: Targeting melanocortin receptors as a novel strategy to control inflammation. Pharmacol Rev 2004;56:1-29.
14. Chiao H, Kohda Y, McLeroy P, Craig L, Housini I, Star RA: Alpha-melanocyte stimulating hormone protects against renal injury after ischemia in mice and rats. J Clin Invest 1997;99:1165-1172.
15. Guarini S, Schioth HB, Mioni C, Cainazzo M, Ferrazza G, Giuliani D, Wikberg JE, Bertolini A, Bazzani C: MC(3) receptors are involved in the protective effect of melanocortins in myocardial ischemia/reperfusion-induced arrhythmias. Naunyn Schmiedebergs Arch Pharmacol 2002;366:177-182.
16. Oprica M, Forslin Aronsson A, Post C, Eriksson C, Ahlenius S, Popescu LM, Schultzberg M: Effects of α-MSH on kainic acid-induced changes in core temperature in rats. Peptides 2002;23:143-149.
17. Bertolini A, Guarini S, Rompianesi E, Ferrari W: α-MSH and other ACTH fragments improve cardiovascular function and survival in experimental hemorrhagic shock. Eur J Pharmacol 1986;130:19-26.
18. Bazzani C, Guarini S, Botticelli AR, Zaffe D, Tomasi A, Bini A, Cainazzo MM, Ferrazza G, Mioni C, Bertolini A: Protective effects of melanocortin peptides in rat myocardial ischemia. J Pharmacol Exp Ther 2001;297:1082-1087.
19. Gatti S, Colombo G, Buffa R, Turcatti F, Garofalo L, Carboni N, Ferla L, Fassati LR, Lipton JM, Catania A: α-Melanocyte-stimulating hormone protects the allograft in experimental heart transplantation. Transplantation 2002;74:1678-1684.
20. Kask A, Mutulis F, Muceniece R, Pahkla R, Mutule I, Wikberg JES, Rago L, Schioth HB: Discovery of a novel superpotent and selective melanocortin-4 receptor antagonist (HS024): evaluation in vitro and in vivo. Endocrinology 1998;139:5006-5014.
21. Emmerson PJ, Fisher MJ, Yan LZ, Mayer JP: Melanocortin-4 receptor agonists for the treatment of obesity. Curr Top Med Chem 2007;7:1121-1130.
22. Hart Sailors ML, Folsom AR, Ballantyne CM, Hoelscher DM, Jackson AS, Linda Kao WH, Pankow JS, Bray MS: Genetic variation and decreased risk for obesity in the Atherosclerosis Risk in Communities Study. Diabetes Obes Metab 2007;9:548-557.
23. Nargund RP, Strack AM, Fong TM: Melanocortin-4 receptor (MC4R) agonists for the treatment of obesity. J Med Chem 2006;49:4035-4043.
24. Cheng YD, Al-Khoury L, Zivin JA: Neuroprotection for ischemic stroke: two decades of success and failure. NeuroRx 2004;1:36-45.
25. O'Collins VE, Macleod MR, Donnan GA, Horky LL, van der Worp BH, Howells DW: 1,026 experimental treatments in acute stroke. Ann Neurol 2006;59:467-477.
26. Dirnagl U: Bench to bedside: the quest for quality in experimental stroke research. J Cereb Blood Flow Metab 2006;26:1465-1478.
27. Sena E, van der Worp BH, Howells D, Macleod M: How can we improve the preclinical development of drugs for stroke. Trends Neurosci 2007;30:433-439.
28. Stroke Therapy Academic Industry Roundtable (STAIR): Recommendations for standards regarding preclinical neuroprotective and restorative drug development. Stroke 1999;30:2752-2758.
29. Durukan A, Tatlisumak T: Acute ischemic stroke: overview of major experimental rodent models, pathophysiology and therapy of focal cerebral ischemia. Pharmacol Biochem Behav 2007;87:179-197.
30. Kopanchuk S, Veiksina S, Petrovska R, Mutule I, Szardenings M, Rinken A, Wikberg JES: Co-operative regulation of ligand binding to melanocortin receptor subtypes: evidence for interacting binding sites. Eur J Pharmacol 2005;512:85-95.