General pharmacology of beraprost sodium. 1st communication: effect on the central nervous system.
Beraprost sodium (sodium (+/-)-(1R*,2R*,3aS*,8bS*)-2,3,3a,8b-tetrahydro-2- hydroxy-1-[(E)-(3S*)-3-hydroxy-4-methyl-1-octen-6-ynyl]-1H- cyclopenta[b]benzofuran-5-butyrate, TRK-100) is an orally active epoprostenol (prostaglandin I2, PGI2) analogue. Its effect on the central nervous system (CNS) was studied. 1. When orally administered in mice, beraprost sodium at 0.3 mg/kg caused a flush of skin, a suppression of spontaneous motility, and a fall of body temperature. At 1 mg/kg and more, it showed obvious sedation, prolongation of hexobarbital hypnosis, and analgesic action in acetic acid-induced writhing test. However, even at 3 mg/kg beraprost sodium neither induced ataxia nor had anticonvulsant activity. Hypothermia was also observed in rabbits at 1 mg/kg (p.o. and i.v.). 2. When intravenously administered, beraprost sodium exerted long-lasting action on the CNS, while its pharmacological effects resembled those of PGI2. 3. Oral administration of beraprost sodium did not inhibit aggregation toxicity induced by methamphetamine (20 mg/kg i.p.) in mice. Beraprost sodium at doses higher than 1 mg/kg enhanced aggregation toxicity induced by methamphetamine (5 mg/kg i.p.), while intracerebral ventricular administration of beraprost sodium failed to enhance it. 4. In rat spinal reflex, intravenous administration of beraprost sodium (0.1 mg/kg) slightly enhanced monosynaptic reflex and at a high dose (1 mg/kg) suppressed polysynaptic reflex. 5. In the rabbit EEG, intravenous administration of beraprost sodium at a high dose (1 mg/kg) showed some effects such as the continuous pattern of wakefulness and a fall in power of the EEG.(ABSTRACT TRUNCATED AT 250 WORDS)
Murata
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Pharmacological Laboratory, Kaken Pharmaceutical Co., Ltd., Tokyo, Japan.
Sakaya
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Hoshino
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Umetsu
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Hirano
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Nishio
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D000700:Analgesics; D000818:Animals; D000927:Anticonvulsants; D001522:Behavior, Animal / Q000187:drug effects; D001831:Body Temperature / Q000187:drug effects; D002490:Central Nervous System / Q000187:drug effects*; D004569:Electroencephalography; D004597:Electroshock; D011464:Epoprostenol / Q000494:pharmacology* / Q000031:analogs & derivatives; D008297:Male; D008694:Methamphetamine / Q000633:toxicity; D051379:Mice; D008813:Mice, Inbred ICR; D009043:Motor Activity / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D011597:Psychomotor Performance / Q000187:drug effects; D011817:Rabbits; D051381:Rats; D012018:Reflex / Q000187:drug effects; D012890:Sleep / Q000187:drug effects
D000700:Analgesics; D000927:Anticonvulsants; D010975:Platelet Aggregation Inhibitors; C048081:beraprost; D008694:Methamphetamine; D011464:Epoprostenol