α-Guanidinoglutaric Acid

α-Guanidinoglutaric Acid is a novel nitric oxide synthase inhibitor with Ki value of 2.69 μM [1].

In the brain, nitric oxide (NO), which is synthesized from L-arginine (Arg) by NO synthase (NOS), acts as both an intra- and an intercellular second messenger, and it may suppress convulsions [1].

α-Guanidinoglutaric Acid (GGA) is a novel nitric oxide synthase inhibitor. GGA was increased in the cobalt-induced epileptic focus tissue in the cerebral cortex of cats [2]. GGA is an endogenous, potent, and non-guanidino nitrogen-substituted NOS inhibitor and that inhibition of nitric oxide biosynthesis may be involved in GGA-induced convulsions. In the cobalt-induced epileptic focus, GGA might inhibit NO production. GGA is a useful tool for the study of the enzyme-substrate relationship of NOS [1].

In rats, GGA injected in the cerebroventricle caused sporadic spike discharges with a latency of several minutes. When Arg was supplemented with GGA, no sporadic spike discharges were observed. These results indicated that Arg elevated the threshold of GGA-induced seizures. The initiation of the seizures induced by GGA was associated with a decrease in the 5-hydroxytryptamine level [1].

References:
[1].  Yokoi I, Kabuto H, Habu H, Mori A. alpha-Guanidinoglutaric acid, an endogenous convulsant, as a novel nitric oxide synthase inhibitor. J Neurochem. 1994 Oct;63(4):1565-7.
[2].  Mori A, Akagi M, Katayama Y, et al. alpha-Guanidinoglutaric acid in cobalt-induced epileptogenic cerebral cortex of cats. J Neurochem. 1980 Sep;35(3):603-5.