The pharmacodynamics of 6-(3-dimethylaminopropionyl)forskolin and a possible metabolite in beagles.
A specific gas chromatography/mass spectroscopy method with a detection limit of 0.1 ng/mL was developed for the measurement of 6-(3-dimethylaminopropionyl)forskolin (1) in beagle plasma. Using this method, plasma concentrations of 1 in beagles given pharmacologically effective intravenous doses of 1.HCl were determined. The observed maximal plasma concentrations rapidly decreased with time, and half-lives of the alpha-phases were < 9 min. Pharmacological effects of 1 on the cardiovascular parameters were simultaneously evaluated in one of the studies. Decreases of the pharmacological effects were slower than decreases in plasma concentration of 1. In addition, 6-(3-methylaminopropionyl)forskolin (N-monodemethyl 1), an expected initial metabolite of 1, was prepared and found to be as pharmacologically active as 1 in beagles. These results and others strongly suggest that a metabolite(s) of 1 contributes to the pharmacological effects of 1 in beagles.
Research Laboratories, Nippon Kayaku Company, Ltd., Tokyo, Japan.
S
S
Kametani
S
S
Matsumoto
T
T
Takahira
M
M
Hosono
Y
Y
Hashimoto
H
H
Horinishi
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D005576:Colforsin / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology; D004285:Dogs; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D007262:Infusions, Intravenous; D007275:Injections, Intravenous; D013268:Stimulation, Chemical; D014665:Vasodilator Agents / Q000493:pharmacokinetics / Q000494:pharmacology*; D017725:Ventricular Pressure / Q000187:drug effects
D014665:Vasodilator Agents; D005576:Colforsin