THE NEUROPROTECTIVE EFFECT OF A POTENT AND SELECTIVE INHIBITOR OF TYPE-I NOS (L-MIN) IN A RAT MODEL OF FOCAL CEREBRAL-ISCHEMIA

OUR newly synthesized delta-(S-methylisothioureido)-L-norvaline (L-MIN ) was shown to have potent inhibitory effects on Ca2+-dependent and co nstitutively expressed neuronal nitric oxide synthase (type I NOS) whe n compared to other commonly recognized NOS inhibitors and produced an IC50 value of 5.7 nM. By contrast, this compound exhibited more than 40-fold weaker inhibitory effects on the other NOS isoforms. Administr ation of L-MIN (0.1, 0.3 and 1 mg kg(-1), i.p.) to rats immediately af ter 2 h middle cerebral artery occlusion and 2 h reperfusion reduced i nfarct size in a dose-dependent manner. These results suggest that typ e I NOS activation has a crucial role in the pathogenic cellular mecha nisms underlying cerebral ischaemia.