XIIIth International Congress of Pharmacology Munich, Germany, July 26–31, 1998 New Drugs Affecting Central Nervous System

Abstract

M. Csejtei et al. (Gedeon Richter Ltd., Budapest, Hungary) reported pharmacological studies with RGH-2716 (8-{4,4-bis(4-fluorophenyl)butyl}-3-1,1-dimethylethyl)-4-methylene-1-oxa-3,8-diazaspiro{4,5}decan-2-one), known also as TDN-345. This drug was reported to protect ischemic brain tissue from energy loss in mice at doses ranging from 3 to 30 mg/kg i.p. At 0.1 to 10 μM it blocked veratridine-induced release of [3H]dopamine or [3H]norepinephrine in rat brain slices. It is thought to prevent elevation of intracellular Ca2+ levels and inhibit voltage-gated Na+ channels in neurons. Gedeon Richter Ltd. is developing RGH-2716 as a memory-enhancing and neuroprotective drug in collaboration with Takeda Chemical Industries of Japan. M. Paroczai et al. (Gedeon Richter Ltd., Budapest, Hungary) reported behavioral effects of RGH 5279 ([–]-transapovincaminic acid-[acetoxy]ethyl ester [3β, 16α]) in rats. RGH-5279 was previously reported to have neuroprotective activity and to inhibit lipid peroxidation in animals. It was now found to antagonize learning and memory deficits induced by diazepam or scopolamine in young rats in the water labyrinth test. It was effective in a retrograde amnesia model at doses as low as 3 mg/kg p.o. It was also effective as a cognition enhancer in rats with basal forebrain lesions. K. Iwasaki et al. (Fukuoka Univ., Japan) reported that the muscarinic (M1) partial agonist SB202026A ({R-(Z)}-α-(methoxyimino)-1-azabicyclo{2,2,2}octane-acetonitrile monohydrochloride) improved deficits in spatial cognition induced by scopolamine, pirenzepine, or experimental brain ischemia in rats. At doses as low as 1 μg/kg i.p., SB202026A decreased errors in radial maze task. The drug is under development for the treatment of Alzheimer’s disease.