The Journal of pharmacy and pharmacology
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J. Pharm. Pharmacol. · Feb 1986
Antagonism of non-depolarising neuromuscular blockade by aminopyridines in cats.
The antagonism of pipecuronium- and vecuronium-induced neuromuscular blockade by 4-aminopyridine (4AP), 3,4-diaminopyridine (3,4AP) and 3-[(dimethylamino)-carbonyl] amino-4-aminopyridine (LF14) were studied in anaesthetized cats during constant infusion of the relaxants. Aminopyridines were administered cumulatively at steady state 90% block level. The ED50 values of 4AP, 3,4AP and LF14 were 243, 106 and 254 micrograms kg-1 in pipecuronium, and 232, 195 and 235 micrograms kg-1 in vecuronium blockade. It has been assumed that in cats the anticurare effect of aminopyridines is mainly a result of K+ channel blockade on motor nerve terminals which enhances the evoked release of acetylcholine.
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J. Pharm. Pharmacol. · May 1985
Disposition of HI-6 oxime in rats after intravenous and intramuscular administration.
The pharmacokinetics of HI-6, a cholinesterase-reactivating oxime, were studied in rats, following intravenous or intramuscular administration. A two-compartment model was used to analyse the intravenous data and a one-compartment open model with first-order absorption was used for intramuscular data. Drug concentration had no influence on rate and extent of absorption of intramuscular injections, and bioavailability was 100%. ⋯ Mean HI-6 plasma concentrations were 140.5 +/- 4.2 micrograms ml-1 3 min after 20 mg ml-1 i.v., with a mean elimination half-life of 65.2 +/- 21 min. Plasma clearance rate was 3.95 +/- 0.93 ml min-1 kg and the apparent volume of distribution was 0.38 +/- 0.17 litre kg-1. The oxime is rapidly distributed in and eliminated by rats when administered intravenously or intramuscularly.
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J. Pharm. Pharmacol. · Dec 1983
Comparative StudyAcenocoumarol and its amino and acetamido metabolites. Comparative pharmacokinetics and pharmacodynamics in the rat.
The elimination, distribution and anticoagulant activity of racemic acenocoumarol, its amino (AM) and acetamido (AA) derivative were determined in male Wistar rats after subcutaneous injection of a single dose of 2 mg kg-1. The effect of daily administration of acenocoumarol on the prothrombin complex activity (PCA) was also investigated. A rapid onset of the hypothrombogenic effect was observed for all three derivatives with the half-life of decline of PCA = 3.6 h. ⋯ The liver to plasma ratio was higher than 1 beyond 10 min after administration. The elimination rate of the drug from liver was slower than from plasma giving an increase in liver to plasma ratio in time. Plasma protein binding was extensive, being the highest for the drug; 1.81, 2.84 and 3.89% free for drug, AM, and AA derivative, respectively.
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J. Pharm. Pharmacol. · Nov 1980
Influence of the sterilization method and of magnesium oxide on the tissue responses in the rat to modified starch glove powders.
The tissue response to samples of a surgical glove powder was assessed from counts of the adhesions and granulomas found 7 and 14 days after introduction into the peritoneal cavity of rats, and by a histological study of affected tissues. Negative control groups treated with no powder and positive controls treated with talc were included. Various sample treatments were implemented to examine the effect of the sterilization method on the tissue response and the influence of magnesium oxide, normally added as a dispersing agent. The glove powder produced less reaction when steam-sterilized than when gamma-irradiated and the presence of magnesium oxide at 2% concentration made no detectable difference.
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J. Pharm. Pharmacol. · Jul 1979
An in vitro study of the effects of calcium on the cardiovascular actions of thiopentone, althesin and ketamine in the rat.
The actions of three intravenous anaesthetics, Althesin, thiopentone and ketamine have been compared on the rat isolated atria and portal vein. Although the three anaesthetics had grossly similar actions on the two preparations. i.e. depression of atrial rate and depression of the amplitude of myogenic activity in the portal vein, there were enough differences to suggest that they produced their effects by different mechanisms. These differences were particularly obvious in interactions with noradrenaline and the effects of changes in calcium ion concentration on the concentration effect relationships for the agents on the atria and portal vein. Generally Althesin was unaffected by changes, but in qualitatively different ways.