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[Stimulation of respiration with Piladox in experimental and clinical conditions during administration of drugs for general anesthesia].

Experimental and clinical studies of the agent Piladox (RGH 2202) were conducted. Experiments on animals (rats, rabbits, mice) demonstrated that Piladox possesses the property of restoring respiration inhibited by narcotic analgesics and some general anesthetics as well as the respiratory-de-priming effect of acute blood loss and is a more effective stimulator of the respiratory center than cordiamine (nikethamide) or corasol. Clinical study of Piladox in 75 patients showed that intravenous infusion of 1 mg/kg of the agent in the awakening period produced a stimulating effect on respiration through increase of its frequency and increase of the respiratory volume. The minute respiratory volume in this case was even greater than the initial values, whereas the CO2 content in the blood and expired air reached the initial level. The hemodynamic values in this period remained generally stable. Piladox does not change the antinociceptive effect of the narcotic analgesics and analgesia in the immediate postoperative period when combined general anesthesia is applied.

Anesthesia, General↗

Effects of 3-trifluoromethyl-alpha-ethylbenzhydrol (RGH-3332), a new enzyme inducer, on the microsomal drug metabolism. Part I.

Intensity and duration of action of several compounds which are metabolized in the liver, are reduced in rats following pretreatment with 3-trifluoromethyl-alpha-ethylbenzhydrol (RGH-3332, Zixoryn), e.g., hexobarbital, methohexitone, glutethimide, hydroxymephenesine, chlorzoxazone, zoxazolamine, ketamine, chlordiazepoxide, diphenylhydantoin, ethylmorphine and pentylenetetrazol, hydroquinone, acenocumarol, respectively. Hypnotic effect of barbital is not altered by RGH-3332. Hexobarbital, meprobamate, mephenesine, nikethamide, canrenone, metyrapone, antipyrine, bromsulphophthalein, inocyanin green, bilirubin disappearance are enhanced, excretion of ascorbic acid is increased after RGH-3332 treatment. The effect of RGH=3332 is inhibited by D,L-ethionine. Hepatic cytochrome P450 concentration is increased following treatment with RGH-3332. Results of in vivo studies proved that 3-trifluoromethyl-alpha-ethylbenzhydrol has enzyme inducing activity.

Animals↗

DRUG-INDUCED CHANGES IN THE LIVER ENDOPLASMIC RETICULUM: ASSOCIATION WITH DRUG-METABOLIZING ENZYMES.

The cellular changes which lead to the increase of drug-metabolizing enzymes following drug administration are explained by correlating new biochemical data with previously reported electron microscopic and pharmacologic observations. Repeated administration of phenobarbital and several other drugs results in a quantitative increase of the smooth endoplasmic reticulum of the liver cell. The marked increase in drug-metabolizing enzymes is found to occur in this enlarged smooth membrane fraction of the endoplasmic reticulum.

Adenosine Triphosphatases↗