The Medical College of Wisconsin, Inc.

Ramesh Babu Boga

Owen W Griffith

Selective and irreversible inhibitors of neuronal isoform of nitric oxide synthase catalyzed production of nitric oxide are L-ornithine or L-lysine derivatives having the formula ##STR1## wherein Q is H or (CH.sub.2).sub.r CH.sub.3 where r ranges from 0 to 15, x is 1 or 2, R' is CH.sub.2 or C(H) (CH.sub.2).sub.y CH.sub.3 where y ranges from 0 to 5, R' is CH.sub.2 or C(H) (CH.sub.2).sub.z CH.sub.3 where z ranges from 0 to 5, R is H or (CH.sub.2).sub.s CH.sub.3 where s ranges from 0 to 5, with none or only one of R, R' and R' providing an alkyl substituent on ornithine or lysine moiety, R.sup.III is OH or is an alkoxy group of 1 to 6 carbon atoms or is an amino acid or peptide attached in amide linkage through its free .alpha.-amino group, and R.sup.IV is --H or an acyl group of 1 to 6 carbon atoms or is an amino acid or peptide attached in amide linkage through its free .alpha.-carboxylate group, and mixtures thereof with corresponding D-isomers. A preferred compound is N.sup.5 -(1-imino-3-butenyl)-L-ornithine. The compounds are useful for treatment of migraine headaches, stroke, pain due to stimulation of nNOS-containing neurons including chronic visceral pain, drug addiction, Parkinson's disease, schizophrenia, and epilepsy.

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Milwaukee, WI, United States of America

Ramesh Babu Boga