Fig 1.

Effects of sildenafil citrate (A) or THIQ MC4R agonist (C) in the mouse cavernous nerve-stimulated model of erectile function. Cavernous nerve stimulation (4.0 v, 16 Hz, 1 ms, for 30 s) was conducted in anesthetized male C57BL/6J mice [n = 6; Mc4r knock-out (−/−) mice were backcrossed six generations with C57BL/6J mice]. Mice were instrumented with corpus cavernosum, carotid artery, and jugular vein catheters for measurement of ICP, MAP, and i.v. compound administration (1 mg/kg for sildenafil, 10 mg/kg for MC4R agonist as a bolus), respectively. The ratio of ICP/MAP (to normalize for any effects on blood pressure) was calculated at −10 min (baseline) followed by 15 and 45 min postdose (sildenafil) or/and 15 min postdose (THIQ); the area under the curve during the 60 s of stimulation was then determined. *, P < 0.05. (B) MCR selectivity profile of THIQ MC4R agonist. EC₅₀ values were determined in a functional activation assay in whole cells measuring cAMP production from cell lines expressing the appropriate MCR (rat Mc3r, 4r, 5r, murine Mc2r, 4r, and human MC1R; species specificity, affecting compound selectivity, has not been observed). The chemical structure of the MC4R agonist is shown.