Journal of the American Pharmaceutical Association (Scientific ed.)最新文献

Quantitative relationships between the dose and incidence, latent period, duration of action, cumulative and minute responses of the apomorphine-induced pecking syndrome are described.

Synthesis of C^I4-labeled hemicholinium No. 3 (HC-3) with a specific activity of 2.788 mc./mM is described. Twenty-four hour studies of rats in metabolism cages indicated 57.5 per cent of an injected dose is excreted in the urine, 15.6 per cent is excreted in the feces, and none is excreted in the expired carbon dioxide. Tissue distribution studies did not show any site of localization in rats.

The effects of reserpine, iproniazid, and their combination on the convulsive threshold, facilitative action, ana seizure pattern of metrazol-treated mice was investigated. The effect of reserpine on metrazol convulsions is a marked decrease in convulsive dose which is accompanied by a reduced seizure latency time in the convulsive pattern with an increasing facilitative action. Iproniazid was found to increase the convulsive dose and lengthen the latency interval. Prior treatment with iproniazid before reserpine reversed the depressive state produced by the latter agent to that of stimulation. This was accompanied by an increased anticonvulsant effect, longer latency interval, and absence of a facilitative action. Treatment with iproniazid after reserpine failed to elicit these effects. These results are compatible with the hypothesis that iproniazid and reserpine produce their effect through a biochemical change, the former by monoamine oxidase inhibition and the latter by release of norepinephrine and other amines from their storage sites in the central nervous system.

A procedure for the determination of sodium pentobarbital and sodium thiopental under rigidly standardized conditions of extraction, using Allen's absorption factor, is described. This method makes possible the reliable quantitative determination of 1 mcg./ml. or smaller concentration differences. In an appendix Allen's absorption factor for sodium pentobarbital is derived.

Isolated mice provide a method of testing tranquilizing and anticonvulsant drugs on abnorml animals. Trifluoroperazine was effective in abolishing head twitch in lower doses than chlorpromazine, showing potency of the added piperazine ring. Phenobarbital inhibited convulsive movements induced by tactile stimulation but did not abolish head twitch.

8-Methoxypsoralen (8-MOP) is well known for its ability to stimulate melanin formation in vitiligo or normal skin if administration is coupled with exposure to sunlight or ultraviolet light. As an approach to studying the mechanism of action of 8-MOP, the latter was incubated with DOPA and exposed to various types of light. Sunlight, white light, or long wave ultraviolet light (3660 Å.) stimulated the oxidation of DOPA in the presence of 8-MOP but not in the absence of the latter. 8-MOP protected DOPA against short wavelength ultraviolet(2540 Å.) although DOPA was oxidized by the latter in the absence of 8-MOP. The photo-oxidation of DOPA in the presence of long wavelength ultraviolet light and 8-MOP was more rapid at pH values above 7 and was completely inhibited by ascorbic acid, cysteine, cysteamine, β-aminoethylisothiuronium bromide HBr, and partially inhibited by sodium thioglycollate. The possible implication of these in vitro observations to the mode of action of 8-MOP in vivo is discussed.

Phenethylbiguanide has been found to form metal complexes with divalent copper and nickel; on the basis of infrared absorption spectra and on theoretical considerations, a revised structure for the metal complexes of biguanides is proposed. Antimicrobial activities of phenethylbiguanide are not affected by divalent copper and nickel but are significantly depressed by iron. The relationship of these findings to the biological mechanisms of action of the compound is discussed.

The solubility of benzoic acid was determined in mixtures of several solvents of varying polarity. The experimental results were compared with the theoretical solubility as calculated from the Hildebrand equation for regular solutions. The theoretical and experimental results agree well in the region where the solubility parameter of the solute approaches that of the solvent mixture.