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ALB-127158(a) is a potent and selective melanin concentrating hormone 1 (MCH₁) receptor antagonist.

MCH₁ receptor

ALB-127158(a) has high affinity for the MCH₁ receptor (7 nM) with good selectivity over a range of other G-protein coupled receptors (GPCRs), ion channels and transporters, including the MCH₂ receptor. In vitro functional assays confirmed that ALB-127158(a) is a potent and selective MCH₁ receptor antagonist.

In a mouse diet induced obesity (DIO) model, ALB-127158(a) produces a significant sustained decrease in body weight and food intake in the range of 5-15 mg/kg bid. The weight reduction is predominantly due to a decrease in fat content. In high fat diet (HFD) rats, ALB-127158(a) produces significant weight loss and food reduction at doses as low as 1.25 mg/kg po. Doses > 1.25 mg/kg po produces weight loss > 6%, maximal weight loss of about 10% in rats is observed at 10 mg/kg. Following single and multiple oral administration of ALB-127158(a), ALB-127158(a) is rapidly absorbed (median t_max attains between 1 and 3 h post dose in lean and overweight/obese subjects) with a trend to decrease over dose suggesting a slower absorption rate of ALB-127158(a) at lower doses. After single doses, ALB-127158(a) has a mean half-life (t_1/2) of 18 to 21 h. Slightly longer mean t_1/2 estimates of approximately 26 h are obtained following multiple dosing in overweight/obese subjects; steady-state plasma ALB-127158(a) is attained within 6 to 8 days of dosing.

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