Camicinal is a selective motilin receptor agonist (pEC50: 7.9).

Motilin receptor:(pEC50)7.9

Camicinal ?had no significant activity at a range of other receptors (including ghrelin), ion channels and enzymes. In rabbit gastric antrum, Camicinal ?300 nmol L 1-10 μmol L 1 caused a prolonged facilitation of the amplitude of cholinergically mediated contractions, to a maximum of 248 ± 47% at 3 μmol L 1. The pEC50 values for motilin, erythromycin and Camicinal ?were, respectively, 10.4 ± 0.01 (n = 770), 7.3 ± 0.29 (n = 4) and 7.9 ± 0.09 (n = 17) . Camicinal ?activated the dog motilin receptor (pEC50 5.79; intrinsic activity 0.72, compared with [Nle13]-motilin) . Camicinal ?was preferred because its initial IC50 values at CYP3A4 were significantly higher than our preferred threshold of 10 μM .

Camicinal (5 mg free base kg 1) increased total fecal weight over the 2-hour post-dose period (21.2 ± 4.5 g; P < 0.05). It induced dose-related phasic contractions (48 and 173 min for 3 and 6 mg kg 1) driven by mean plasma concentrations >1.14 μmol L 1. After the effects of GSK962040 faded, migrating motor complex (MMC) activity returned. MMC restoration was unaffected by 3 mg kg 1 GSK962040 but returned 253 min after dosing at 6 mg kg 1, compared to 101 min after saline (n = 5 each). The oral bioavailability (Fpo) of Camicinal (GSK962040) was 48 ± 13%. Camicinal had a long-lasting effect (T1/2 = 46.9 ± 5.0 min at 3 μM) compared with the short-lived effect of [Nle13]motilin (T1/2 = 11.4 ± 1.5 min at 0.3 μM). Camicinal strongly facilitated cholinergic activity in the antrum, with lower activity in the fundus and small intestine.