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J Infect Dis. 1975 Dec;132(6):611-16.
Inhibitory effects of antihistamines and antiserotonins on the bone marrow reactions produced by Escherichia coli endotoxin in mice.

Hirata M.

The bone marrow reactions (that is, decrease of nucleated cell counts and increase of red blood cell counts) of mouse bone were observed 1 hr after injection of endotoxin and peaked after 18 hr. These reactions were significantly inhibited when diphenhydramine, promethazine (antihistamines), chlorpromazine (antiserotonin), or cyproheptadine (antihistamine and antiserotonin) was given 30 min before endotoxin. Such bone marrow reactions were also induced with histamine or serotonin and peaked 1 hr after administration. The histamine-induced changes were inhibited by prior treatment with diphenhydramine. These reactions were also produced by injection of a small amount of both histamine and serotonin, whereas no change was found when mice were given a single injection of a larger dose of histamine or serotonin. These results indicate that histamine and serotonin released in mice at the initial stage after endotoxin synergistically trigger the bone marrow reactions, which then continue in the presence of further mediators. Antihistamines and antiserotonins are considered to hinder the whole process of reactions produced by endotoxin.

online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=442&dopt=Abstract




Biol Pharm Bull. 1993 Sep;16(9):847-51.
Metabolic formation of dimethylamine and methylamine from basic drugs containing N-methyl group: a newly established chromatographic assay and its application to the determination of deaminase activity.

Yamada H, Shimizudani T, Hatsumura M, Oguri K, Yoshimura H.

Faculty of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.

A new method of assaying deaminase activity was established in which methylamine and/or dimethylamine formed from drugs containing N,N-dimethyl or N-methyl group were derivatized with phenylisothiocyanate to phenylthiourea derivatives. After purification with Sep-PAK C18 cartridge, the derivatives were separated by a reversed phase high-performance liquid chromatography monitored by ultraviolet absorption. The recoveries and determination limits of methylamine and dimethylamine were over 55% and about 0.4 nmol/ml of incubation mixture, respectively. The method was used to measure the deaminase activities of liver microsomes of rats, rabbits and guinea pigs for 11 drugs. Of the compounds tested, diphenhydramine and diltiazem are deaminated with microsomes from all the above animal species; rat and rabbit liver microsomes also well deaminated promethazine. Most other drugs such as chlorpromazine, promazine, imipramine, amitriptyline and tetracaine were found to be poor substrates. In general, dimethylamine but not methylamine was the predominant metabolite formed from drugs containing N,N-dimethylamino group. The results also suggested that the deamination of these compounds takes place mainly via a one step mechanism, thus implying that the sequential reaction consisting of N-demethylation and elimination of ammonia is of minor importance. The relation between in vitro deaminase activity and the extent of the in vivo deamination for drugs is discussed.

online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8268849&dopt=Abstract




J Pharm Biomed Anal. 1993 Oct;11(10):893-6.
Kinetic fluorimetric determination of promethazine by a stopped-flow mixing technique.

de la Pena L, Gomez-Hens A, Perez-Bendito D.

Department of Analytical Chemistry, Faculty of Sciences, University of Cordoba, Spain.

The oxidation of promethazine to its corresponding fluorescent sulphoxide was used to develop a novel kinetic fluorimetric method for the determination of this drug. The use of a stopped-flow mixing technique makes use of an oxidizing reagent unnecessary because the oxidation is rapidly carried out by dissolved oxygen. The method is simple and fast as it only requires a few seconds to obtain kinetic data which allows ready application to routine analyses. The calibration graph is linear over the range 0.5-80 micrograms ml-1 and the precision (%RSD) is close to 2%. The method was applied to the determination of promethazine hydrochloride in two pharmaceutical preparations.

online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8305592&dopt=Abstract













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