| abstract |
Guanidino substituted arginines or homoarginines based on monoalkyl carbon-substituted ornithines or lysines, having the formula (* CHEMICAL STRUCTURE *) wherein R is (CH2)yCH3 or H, R' is CH2 or C(H)(CH2)yCH3, and R" is CH2 or C(H)(CH2)yCH3, with y ranging from 0 to 5, and x is 0 or 1 and Q is an alkyl group containing from 1 to 6 carbon atoms or NH2 or NO2, and only one of R, R' and R" providing an alkyl substituent on the ornithine or lysine moiety. Preferred compounds are (alpha)-methyl-N(omega)-methyl-DL-arginine, RS-(beta)-methyl-N(omega)-methyl-DL-arginine, RS-(gamma)-methyl-N(omega)-methyl-DL-arginine, (alpha)-methyl-N(omega)-amino-DL-arginine, RS-(beta)-methyl-N(omega)-amino-DL-arginine, RS-(gamma)-methyl-N(omega)-amino-DL-arginine, (alpha)-methyl-N(omega)-nitro-DL-arginine, RS-(beta)-methyl-N(omega)-nitro-DL-arginine, and RS-(gamma)-methyl-N(omega)-nitro-DL-arginine. A composition includes said compound together with a pharmaceutically acceptable carrier. Methods of use are directed to delivering said compound to inducible nitric oxide synthase to inhibit the ability of the enzyme to catalyze the conversion of arginine to nitric oxide, to administering said compound to inhibit pathological overproduction of nitric oxide from arginine and to administering said compound to a subject having systemic hypotension due to the pathological overproduction of nitric oxide and an (alpha)1 adrenergic agonist to increase blood pressure in the subject to a clinically acceptable level. |