title: Acute effects of oral pyridostigmine bromide on conditioned operant performance in rats.
abstract: Pyridostigmine bromide (Pyr), the current drug of choice in the management of myasthenia gravis, has been suggested for use in Alzheimer's dementia, and as a prophylactic treatment for intoxication with organophosphate cholinesterase inhibitors. The present study was undertaken to evaluate the dose-response and time-course effects of acute oral administration of Pyr over a broad dose range (3-40 mg/kg) on the lever pressing of rats maintained under a multiple fixed-ratio (FR-20) time-out schedule of reinforcement for water reward. The drug produced a dose-dependent biphasic response depression in the overall rate of FR responding. Low doses of Pyr (less than or equal to 12 mg/kg) that caused no gross signs of toxicity only moderately decreased rates of responding, primarily due to a decrease in response rates. Whereas high doses of Pyr (greater than 24 mg/kg) which produced overt signs of peripheral cholinergic intoxication markedly suppressed overall responding, primarily due to cessation of responding. The lowest effective dose of performance disruption was 6 mg/kg, and the ED50 was calculated as 23.3 (17.9-28.7) mg/kg. The time-course data of performance disruption showed that low doses of Pyr (less than or equal to 12 mg/kg) had an onset latency within 40-80 min and a duration of 20-80 min, whereas high doses (greater than or equal to 24 mg/kg) had an onset latency of 20-40 min and a duration greater than 80 min. These results suggest the recommended human therapeutic or prophylactic regimen of 30-120.mg Pyr, orally taken each 8 hours, might adversely affect behavioral performance.
authors.affiliation: Chemical Systems Division, CSIST, Lung-Tan, Taiwan, R.O.C.
authors.forename: J H
authors.initials: JH
authors.lastname: Shih
authors.forename: W F
authors.initials: WF
authors.lastname: Liu
authors.forename: S F
authors.initials: SF
authors.lastname: Lee
authors.forename: J D
authors.initials: JD
authors.lastname: Lee
authors.forename: C
authors.initials: C
authors.lastname: Ma
authors.forename: C H
authors.initials: CH
authors.lastname: Lin
mesh_terms: D000284:Administration, Oral; D000544:Alzheimer Disease / Q000188:drug therapy; D000818:Animals; D003216:Conditioning, Operant / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D008297:Male; D011729:Pyridostigmine Bromide / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012055:Reinforcement Schedule
chemical_list: D011729:Pyridostigmine Bromide