Camicinal hydrochloride (GSK962040 hydrochloride) is a selective motilin receptor agonist with a pEC50 of 7.9.

Motilin receptor:7.9 (pEC50)

Camicinal hydrochloride activated the dog motilin receptor (pEC50 5.79; intrinsic activity 0.72, compared with [Nle13]-motilin) [1]. Camicinal hydrochloride was preferred because its initial IC50 values at CYP3A4 were significantly higher than our preferred threshold of 10 μM [2]. Camicinal hydrochloride had no significant activity at a range of other receptors (including ghrelin), ion channels, and enzymes. In rabbit gastric antrum, Camicinal hydrochloride (300 nmol/L -10 μmol/L) caused prolonged facilitation of the amplitude of cholinergically mediated contractions, to a maximum of 248 ± 47% at 3 μmol/L. The pEC50 values for motilin, erythromycin and Camicinal hydrochloride were, respectively, 10.4 ± 0.01 (n = 770), 7.3 ± 0.29 (n = 4) and 7.9 ± 0.09 (n = 17) [4].

Camicinal hydrochloride induced phasic contractions, the duration of which was dose-related (48 and 173 min for 3 and 6 mg/kg), driven by mean plasma concentrations >1.14 μmol/L. After the effects of Camicinal hydrochloride faded, migrating motor complex (MMC) activity returned. Migrating motor complex restoration was unaffected by 3 mg/kg Camicinal hydrochloride but at 6 mg/kg, MMCs returned 253 min after dosing, compared with 101 min after saline (n = 5 each) [1]. The oral bioavailability (Fpo) of Camicinal hydrochloride was found to be 48 (13%. Camicinal hydrochloride shows a long-lasting effect (T1/2) 46.9 (5.0 min at 3 μM) when compared with the short-lived effect of [Nle13]motilin (T1/2 ) 11.4 (1.5 min at 0.3 μM) [2]. Camicinal hydrochloride (5 mg/kg) also produced an increase in total faecal weight over the 2-h postdose period (21.2 ± 4.5 g; P < 0.05) [4]. Camicinal hydrochloride strongly facilitated cholinergic activity in the antrum, with lower activity in the fundus and small intestine only [4].