Selective neuronal nitric oxide synthase inhibitors and the prevention of cerebral palsy.

ABSTRACT:

Objective

To design a new class of selective neuronal nitric oxide synthase (NOS) inhibitors, and demonstrate that administration in a rabbit model for cerebral palsy (CP) prevents hypoxia-ischemia-induced deaths and reduces the number of newborn kits exhibiting signs of CP.

Methods

We used a novel computer-based drug design method called fragment hopping to identify new chemical entities, synthesized them, and conducted in vitro enzyme inhibition studies with the three isozymes of NOS and in vivo experiments to monitor cardiovascular effects on pregnant rabbit dams, NOS activity, and NO(x) (NO and NO(2)) concentration in fetal brain, and assess neurobehavioral effects on kits born to saline- and compound treated dams.

Results

The computer-based design led to the deve

SUBMITTER: Ji H 

PROVIDER: S-EPMC2658647 | biostudies-literature | 2009 Feb

REPOSITORIES: biostudies-literature