Orally administered H-Dmt-Tic-Lys-NH-CH2-Ph (MZ-2), a potent mu/delta-opioid receptor antagonist, regulates obese-related factors in mice.
Orally active dual mu-/delta-opioid receptor antagonist, H-Dmt-Tic-Lys-NH-CH(2)-Ph (MZ-2) was applied to study body weight gain, fat content, bone mineral density, serum insulin, cholesterol and glucose levels in female ob/ob (B6.V-Lep<ob>/J homozygous) and lean wild mice with or without voluntary exercise on wheels for three weeks, and during a two week post-treatment period under the same conditions. MZ-2 (10mg/kg/day, p.o.) exhibited the following actions: (1) reduced body weight gain in sedentary obese mice that persisted beyond the treatment period without effect on lean mice; (2) stimulated voluntary running on exercise wheels of both groups of mice; (3) decreased fat content, enhanced bone mineral density (BMD), and decreased serum insulin and glucose levels in obese mice; and (4) MZ-2 (30 microM) increased BMD in human osteoblast cells (MG-63) comparable to naltrexone, while morphine inhibited mineral nodule formation. Thus, MZ-2 has potential application in the clinical management of obesity, insulin and glucose levels, and the amelioration of osteoporosis.
Marczak
Ewa D
ED
Medicinal Chemistry Group, Laboratory of Pharmacology, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. marczake@niehs.nih.gov
Jinsmaa
Yunden
Y
Myers
Page H
PH
Blankenship
Terry
T
Wilson
Ralph
R
Balboni
Gianfranco
G
Salvadori
Severo
S
Lazarus
Lawrence H
LH
D000273:Adipose Tissue / Q000187:drug effects; D000284:Administration, Oral; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D015519:Bone Density / Q000187:drug effects; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D004435:Eating / Q000187:drug effects; D005260:Female; D006801:Humans; D007328:Insulin / Q000097:blood; D051379:Mice; D008903:Minerals / Q000378:metabolism; D009765:Obesity / Q000097:blood / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D009842:Oligopeptides / Q000008:administration & dosage* / Q000494:pharmacology* / Q000627:therapeutic use; D010006:Osteoblasts / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D010805:Physical Conditioning, Animal; D017465:Receptors, Opioid, delta / Q000037:antagonists & inhibitors*; D017450:Receptors, Opioid, mu / Q000037:antagonists & inhibitors*; D012965:Sodium Chloride / Q000008:administration & dosage
C533065:H-Dmt-Tic-Lys(Z)-NH-CH2-Ph; D007328:Insulin; D008903:Minerals; D009842:Oligopeptides; D017465:Receptors, Opioid, delta; D017450:Receptors, Opioid, mu; D012965:Sodium Chloride