|Budget Amount *help
¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 1993: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1992: ¥1,300,000 (Direct Cost: ¥1,300,000)
Some novel and potent metabotropic glutamate receptor (mGluR) agonists, such as L-CCG-I [2S,1'S,2'S)-2-(carboxycyclopropyl)glycine], and its analogues, DCG-IV[(2S,1'R,2'R,3'R)-2-(2,3-dicarboxycylopropyl)glycine] and cis-MCG-I[(2S,1'S,2'R,3'R)-2-(2-carboxy-3-methoxymethylcyclopropyl)glycine], were newly found in the present project. They were more potent and selective than a known mGluR agonist, (1S,3R)-ACPD.They have central depressant actions in the rat when they were intraventricularly administered at relarively low doses. L-CCG-I effectively inhibited kindling seizures, and intraventricular administration of DCG-IV effectively prolonged the recovery from halothane anesthesia in the rat. After prolonged intraventricular infusion of DCG-IV(24-240 pmoles/rat, 17hrs) to the rat, 2 nmoles of kainic acid(KA) was infused into the rat ventricle. The KA-induced limbic motor seizures and neuron damage in the hippocampus CA3 area, amygdala and septum were considerably inhibited by pre-infusion of DCG-IV into the rat ventricle. In particular, fairly low doses of DCG-IV were effective, although relatively high doses of DCG-IV per se induced selective neuron damage in the rat cingulate cortex. One shot of DCG-IV did not inhibit so much limbic motor seizures and neuron damage.