Richard A. Seibert

Effect of certain drugs on the incidence of seasickness.

Several drugs were tested, some of them for the first time, against seasickness in military personnel on transport ships on the North Atlantic ocean. All of the drugs were given three fimes a day. Of the new ones tested phenglutarmide, 2.5 mg., and cinnarazine, 7.5 mg., were significantly effective on a single trip. Somewhat less effective were atropine and orphenadrine.

Effects of 3-methylcholanthrene and some related compounds upon the benzpyrene hydroxylase activity in fetal rat liver explants.

Abstract The addition of 3-methylcholanthrene (3-MC) or some of its derivatives to expiants of fetal rat liver caused a reproducible “induction” of benzpyrene (BP) hydroxylase. In fresh explants, a lag of 6–12 hr was observed, whereas a more immediate increase in enzyme activity was noted when 3-MC was added to 40-hr preincubated cultures. The addition of 3-MC and 1-keto-3-MC (10 −5 M in the medium) caused a 4-fold elevation in BP-hydroxylase, while the 1-hydroxy and the cis-11,12-dihydroxy-11, 12-dihydro derivatives produced a stimulatory activity of only 2,7- and 2-fold respectively. The most potent compound in this regard was the trans-1,2-dihydroxy-3-MC; its administration resulted in a 6.7-fold increase in enzyme activity. This study points out certain advantages of studying the induction phenomenon in this system in vitro .

Pharmacokinetics of guanazole in man

Guanazole, 3,5‐diamino‐1,2,4‐triazole, synthesized nearly a century ago, has recently been shown to have antitumor properties. In patients with cancer, intravenous doses ranging from 3.5 to 10 gm per square meter of body surface area have been used. It was found that the 15 minute plasma level declines to one‐half in 1 to 2 hours. After 4 to 6 hours the plasma half‐life is 5 to 10 hours. The drug is eliminated almost quantitatively in the urine in 24 hours. No metabolites could be detected in the perfusate or bile of the isolated perfused rat liver preparation, suggesting that the drug itself rather than a metabolite is responsible for the antitumor activity.

Effects of galactoflavin-induced riboflavin deficiency upon rat hepatic cell ultrastructure.

SummaryThe primary cytoplasmic effect of galactoflavin-induced riboflavin deficiency upon rat liver cells involved focal sites of degradation which were manifested by the formation of membranous whorls. The nuclear effect of riboflavin deficiency concerned fluctuations in the total number of perichromatin granules per nucleus. These granules increased in number during the deficiency reaching a peak at three weeks. Nucleoli appeared compact with no evidence for segregation of nucleolar components. The possible correlation between increased synthesis of perichromatin granules and altered protein synthesis is discussed.

Metabolism of Methocarbamol (Robaxin) in the Isolated Perfused Rat Liver and Identification of Glueuronides

1. Permethylation and g.l.c.-mass spectrometric analysis of bile from an isolated rat liver perfusion to which methocarmol was added showed seven components not present in control bile: methocarbamol, glucuronides of methocarbamol and desmethyl-methocarbamol, and four glucuronides of hydroxylated methocarbamol metabolites. 2. An interesting rearrangement of a methyl group has been found in the mass spectrum of 3-(2-methoxyphenyloxy)-1,2-dimethoxypropane, the permethylation product from methocarbamol.

Effects of the 1-keto and 1-hydroxy derivatives of 3-methylcholanthrene upon liver drug metabolizing enzyme activity.

Abstract The effects of 2 oxidized derivatives of 3-methylcholanthrene upon the drug metabolizing enzyme system in liver were determined. 3-Methylcholanthrene-1-one was 60 per cent as effective as the parent compound in stimulating the activity of benzpyrene hydroxylase in liver after intraperitoneal administration, while the 1-hydroxy derivative was ineffective in this regard. The administration of 3-methylcholanthrene to rats resulted in a 3-fold increase in the ability of liver microsomes to metabolize zoxazolamine, while the administration of the 1-keto and the 1-hydroxy derivatives produced a stimulatory activity of only 2- and 1·7-fold respectively. The rates of zoxazolamine metabolism were correlated with the duration of zoxazolamine-induced paralysis observed after administration of the methylcholanthrene derivatives to rats.

Asynchrony of erythroblast maturation induced by riboflavin deficiency

SummaryUltrastructural studies indicate that galactoflavin-induced riboflavin deficiency induces asynchrony of rat erythroblast maturation. During the latter stages of maturation erythroblasts retain significantly larger numbers of ribosomes as compared to control cells. Nucleoli are not evident in erythroblasts whose nuclei indicate cells in the latter stages of development. Membrane whorls develop within the mitochondria of plasma cells, eosinophils and neutrophils during the fifth week of riboflavin deficiency. No further evidence of degeneration was noted among aditional cell organelles.