Co-administration of SR141716 with peptide YY3-36 or oxyntomodulin has additive effects on food intake in mice.
BACKGROUND
SR141716 has been shown to significantly inhibit food intake and reduce body weight by antagonizing CB(1) receptors. The gut hormones peptide YY(3-36) (PYY(3-36)) and oxyntomodulin (OXM) inhibit food intake through Y(2) and Glucagon-Like-Peptide (GLP)-1 receptors respectively.


OBJECTIVE
To determine the effects of co-administration of SR141716 with either PYY(3-36) or OXM in mice on food intake.


METHODS
Mice (n = 14 per group) were fasted for 16 h prior to study days and given two intraperitoneal injections: study 1, vehicle-saline, SR141716-saline, vehicle-PYY3-36 or SR141716-PYY3-36; study 2: vehicle-saline, SR141716-saline, vehicle-OXM or SR141716-OXM. Food was returned and measured following injections.


RESULTS
Co-administration of SR141716-PYY(3-36) or SR141716-OXM showed greater inhibition in food intake when compared with administration of SR141716, PYY(3-36) or OXM alone.


CONCLUSIONS
Our data show that SR141716 in combination with PYY(3-36) or OXM reduces food intake additively in mice.
White
N E
NE
Department of Metabolic Medicine, Faculty of Medicine, Imperial College London, Hammersmith Hospital, London, UK.
Dhillo
W S
WS
Liu
Y-L
YL
Small
C J
CJ
Kennett
G A
GA
Gardiner
J V
JV
Ghatei
M A
MA
Bloom
S R
SR
D000818:Animals; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D004435:Eating / Q000187:drug effects* / Q000502:physiology; D005215:Fasting / Q000378:metabolism / Q000523:psychology; D051379:Mice; D009765:Obesity / Q000517:prevention & control; D053772:Oxyntomodulin / Q000008:administration & dosage / Q000494:pharmacology*; D010446:Peptide Fragments; D019894:Peptide YY / Q000008:administration & dosage / Q000494:pharmacology*; D010880:Piperidines / Q000008:administration & dosage / Q000494:pharmacology*; D011720:Pyrazoles / Q000008:administration & dosage / Q000494:pharmacology*; D000077285:Rimonabant; D016896:Treatment Outcome
D053772:Oxyntomodulin; D010446:Peptide Fragments; D010880:Piperidines; D011720:Pyrazoles; D019894:Peptide YY; C061785:peptide YY (3-36); D000077285:Rimonabant