PMC

Mean 17-desacetyl norgestimate plasma concentration–time profile following a 0.250 mg oral dose of norgestimate in human subjects.

ESI product ion mass spectra of the precursor ions of (A) 17-desacetyl norgestimate and (B) 17-desacetyl norgestimate D6.

Representative wire myograph recording (A) illustrating the effect of norgestimate on L-NAME treated intact aortic rings pre-contracted with phenylephrine. Compounds were applied as indicated in the perfusate. Acetylcholine (Ach) was applied to demonstrate the absence of endothelium-dependent vasorelaxation. Higher norgestimate concentrations could not be tested due to the limited solubility of the compound. Concentration-response curve of norgestimate-induced vasorelaxation (B). Norgestimate-induced relaxation was expressed as percentage of the phenylephrine-induced tension prior to norgestimate application. The solid line represents the best fit of the data to the Hill model with: y₀ = −4.26%, y₁ = 84.8%, and n = 0.93. Data represent means ± SEM (n = 6).

OAG-induced changes of [Ca²⁺]_i in fluo-4-loaded TRPC3 CHO cells (A) and TRPC6 HEK-FITR cells (C) were measured in 96-well plates using a fluorometric imaging plate reader. Pre-incubation of cells with 30 µM norgestimate (NG) significantly reduced TRPC3 and −6 mediated Ca²⁺ entry. Representative fluorescence traces are shown. Concentration-response curves for inhibition of TRPC3 (B) and TRPC6 (D) by norgestimate were derived from the area under the fluorescence curves for each given concentration. The solid lines represent the best fit of the data to the Hill model with slopes of n = 1.67 (TRPC3) and n = 0.97 (TRPC6). Means ± SEM of 3 wells (B) or 4 wells (D) are shown. The chemical structure of norgestimate is illustrated in B.