| 摘要 |
<p>Use of 4-substituted 2-pyrrolidinone derivatives (I) as drugs, specifically for reducing extracellular glutamate levels, is new. - Use of 2-pyrrolidinone derivatives of formula (I) and their salts and prodrugs as therapeutic active agents is new. - R1, R2 = H, OH, NH2, 1-10C alkoxy, 1-10C alkyl or 1-10C alkylamino, but not both H; - or CR1R2 = 5-10 membered saturated or unsaturated ring, optionally containing 1 or 2 O, S or N heteroatom(s) and optionally substituted by 1-3 of OH, NH2, 1-4C alkyl, 1-4C alkoxy and 1-4C alkylamino; - R3-R6 = H, OH, NH2, 1-10C alkyl, 1-10C alkoxy, 1-10C alkylamino or 6-10C aryl; - R7 = H, 1-10C alkyl or 1-10C acyl. - An INDEPENDENT CLAIM is also included for the use of (I) or their salts for the treatment and/or prophylaxis of diseases associated with elevated extracellular glutamate levels. - ACTIVITY - Neuroprotective; glutamate neurotoxicity inhibitor. - In a glaucoma model of neurodegeneration in rats, 8-aza-spiro (5,4) decan-9-one (Ia) was administered at 50 mg/kg i.p. before and after increase of intraocular pressure. The average degree of survival of retinal ganglion cells 14 days later was 35.0%, compared with 17.4% for saline-treated controls. No deaths were observed in the (Ia)-treated group in 14 days. - MECHANISM OF ACTION - Glutamatergic neurotransmission inhibitor. (I) reduce extracellular glutamate levels and inhibit the depolarisation and over-stimulation of post-synaptic cells, e.g. by presynaptically released glutamate.</p> |
