Pharmacological study of nicergoline. Effects on regional cerebral blood flows and arterial carbon dioxide and oxygen pressure and pH in rats under cyanide-induced histotoxic anoxia.
1. Effects of nicergoline (CAS 27848-84-6) and two alpha-adrenoceptor antagonists on changes in the regional frontal cortex and brainstem blood flow (rFCBF and rBSBF), as determined by the hydrogen clearance method, PaCO2, PaO2 and pHa, were studied in immobilized and ventilated rats under KCN-induced histotoxic anoxia. In the control group of rats in the early anoxic phase 3 min after the injection of a sublethal dose of KCN (3 mg/kg i.v.), rFCBF became markedly decreased, and was associated with a fall in PaCO2, a rise in PaO2 and an elevation in pHa (metabolic alkalosis); but rBSBF remained unchanged. Twenty to 30 min after KCN, the lowered PaCO2 and the raised PaO2 returned to pre-KCN levels, but pHa declined markedly (metabolic acidosis). During this recovery period, the marked increases in both rFCBF and rBSBF were produced. These anoxic changes disappeared 60 min after KCN. Nicergoline (8 and 32 micrograms/kg i.v.) improved the lowered PaCO2, the raised PaO2 and the metabolic alkalosis, and also prevented the marked decrease of rFCBF in the early anoxic phase. The drug also promoted recovery of the raised PaO2, improved the metabolic acidosis, and prevented the marked increases in rFCBF and rBSBF during the recovery period. These effects of nicergoline as well as those of dihydroergotoxine (32 and 128 micrograms/kg, i.v.) were dose-dependent. Phentolamine (128 micrograms/kg i.v.), however, did not affect the anoxic changes in rFCBF, rBSBF, or the above humoral factors after KCN.(ABSTRACT TRUNCATED AT 250 WORDS)
Shintomi
K
K
Safety Research Laboratory, Tanabe Seiyaku Co., Ltd., Osaka, Japan.
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001933:Brain Stem / Q000098:blood supply; D002245:Carbon Dioxide / Q000097:blood*; D015687:Cell Hypoxia / Q000187:drug effects / Q000502:physiology*; D002540:Cerebral Cortex / Q000098:blood supply; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D003486:Cyanides / Q000633:toxicity; D004088:Dihydroergotoxine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006339:Heart Rate / Q000187:drug effects; D006863:Hydrogen-Ion Concentration; D008297:Male; D009530:Nicergoline / Q000494:pharmacology*; D010100:Oxygen / Q000097:blood*; D010646:Phentolamine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains
D003486:Cyanides; D004088:Dihydroergotoxine; D002245:Carbon Dioxide; D009530:Nicergoline; D010100:Oxygen; D010646:Phentolamine