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R R Levine

Publications and source records attributed to R R Levine.

8 recordsLinked to original sources
PubMed1979

The role of plasma concentrations in the use of tricyclic antidepressant drugs.

1. The range of tricyclic antidepressant plasma levels (or doses) needed for therapeutic response remains largely unresolved, since quantal plasma concentration (or dose)--response relationships have not been clearly defined for either therapeutic or nontherapeutic effects. 2. The fact that certain patients apparently became more depressed at higher plasma levels must be balanced against the facts that "depression" is a mixture of disorders as yet poorly distinguishable and that tricyclic antidepressants have multiple pharmacologic effects. 3. There is presently no justification for routinely monitoring tricyclic antidepressant plasma levels, even though, as for any drug, such determinations are justifiable in patients who are unresponsive or show signs of toxicity. 4. Plasma level determinations can never replace sound clinical judgment and dosage adjustment for individual patients.

Amitriptyline↗
PubMed1979

Methods for the analysis of intestinal function.

The intestinal tract, an organ of considerable complexity, requires application of numerous techniques for analysis of its physiology and perturbations by toxicologic agents. This review describes the methodology of importance in analysis of the absorptive function of the intestine and the transit of intestinal contents. Methods for studying absorption are categorized according to the technique for administering the test substance such as inclusion in the diet or by gastric and intestinal placement and the method of quantitating the degree of absorption such as determining the appearance of a test substance in systemic fluids or its disappearance from its site of administration in the intestine. In vitro techniques which have no in vivo analogs, such as the use of the everted sac, are briefly described and their limitations emphasized. Procedures of importance in the clinical diagnosis of malabsorption or in the experimental analysis of absorptive function in man are included and distinguished from techniques used in animal models. In addition, methods for studying aspects of gastrointestinal motility, including the use of luminal markers and analysis of the contractile and electrical activity of intestinal smooth muscle, are reviewed.

Animals↗
PubMed1978

Regeneration of olfactory axons and synapse formation in the forebrain after bulbectomy in neonatal mice.

We removed the right olfactory bulb in neonatal mice, leaving the bulb on the left side intact as an internal control. At 5 days of survival time, we observed that the right cerebral hemisphere was displaced forward to occupy the region made vacant by removal of the bulb. The frontal cortex was, consequently, in close proximity to the lamina cribrosa. As a result of bulb ablation and severance of the fila olfactoria, the sensory perikarya underwent total retrograde degeneration, which peaked at 8 days. New neurons differentiated in the neuroepithelium from basal stem cells and, at 30 days of survival, mature sensory neurons were reconstituted. These new elements sent their axons through the lamina cribrosa to reach the protruding cerebral hemisphere, penetrating it and forming glomeruli-like structures directly in the host tissue. The "glomerulization" of the sensory fibers persisted and actually expanded between 60 and 120 days. The new glomeruli were organized intimately within the brain tissue, and large neurons of the cortex were observed to be in close proximity. Ultrastructural observations of the newly formed glomeruli demonstrated that typical sensory axon terminals profusely branched and synapsed with unidentified postsynaptic processes that penetrated the glomeruli from the surrounding cerebral tissue.

Animals↗
PubMed1975

Studies of the enterohepatic circulation of morphine in the rat.

The disposition of 14C-morphine was studied after gastrointestinal and subcutaneous administration to female Sprague-Dawley rats. Morphine was found to be rapidly and nearly completely absorbed from the small intestine. After s.c. administration, approximately half the 5 mg/kg dose of morphine was excreted via the bile into the intestinal tract, largely as morphine glucuronide. Unlike morphine, the glucuronide conjugate in bile was poorly absorbed from the small intestine where its hydrolysis occurred slowly. After administration into the cecum, however, hydrolysis of the conjugate was rapid, and the rate of absorption of radioactive material was similar to that of free morphine. Treatment of rats with lincomycin (500 mg/1 in drinking water and 25 mg twice a day by gastric intubation for 4 days) significantly decreased cecal hydrolysis of the conjugate and the cecal absorption of radioactive material. Lincomycin treatment also increased fecal excretion of the conjugate in rats given morphine s.c. (5 mg/kg). These findings indicated that hydrolysis of morphine glucuronide is dependent upon the status of enteric bacteria and is a prerequisite to the enterohepatic circulation of morphine. In addition, after lincomycin treatment, a greater percentage of radioactivity excreted in the urine was associated with free morphine. This finding could be expained by the demonstration of pH dependence of renal excretion of morphine and a first-pass effect for this drug.

Ammonium Chloride↗
PubMedDate not supplied

The gastrointestinal absorption of methadone in the rat.

The absorption of dl-methadone from the gastrointestinal tract of the Sprague-Dawley rat was examined by the in vivo segment technique. Duodenal absorption, measured as a function of time and dose, followed first-order kinetics with a half-life of 15.6 min. Absorption was not influenced by prior or concomitant administration of a variety of drugs. Absorption from other regions of the intestine was similar to that from the duodenum; in contrast, absorption from the stomach was markedly slower. Gastric absorption was increased by alkalinization of stomach contents but was still considerably slower than from the duodenum. Gastric emptying of methadone appears to be the rate-limiting step in the overall gastrointestinal absorption of the drug, since the rate of emptying following intubation of the drug into the stomach was also considerably slower than the rate of duodenal absorption.

Animals↗