Drugs online research references
J Natl Cancer Inst. 1994 May 18;86(10):770-5.
Enhanced cancer growth in mice administered daily human-equivalent doses of some H1-antihistamines: predictive in vitro correlates.
Brandes LJ, Warrington RC, Arron RJ, Bogdanovic RP, Fang W, Queen GM, Stein DA, Tong J, Zaborniak CL, LaBella FS.
Department of Medicine, Manitoba Institute of Cell Biology, University of Manitoba, Winnipeg, Canada.
BACKGROUND: Present studies of drug-induced tumor growth promotion have evolved from earlier investigations into the mechanism of action of N,N-diethyl-2-[4-(phenylmethyl)phenoxy[ethanamine.HCl, a tamoxifen derivative which potently inhibits lymphocyte mitogenesis in vitro and stimulates tumor growth in vivo. It is thought that potency to bind to intracellular histamine receptors (HIC), some of which are on cytochromes P450, may correlate with tumor growth-promoting activity. PURPOSE: We assessed the effectiveness of five in vitro assays in predicting in vivo tumor growth stimulation by the H1-antihistamines loratadine, astemizole, cetirizine, hydroxyzine, and doxylamine. METHODS: Potency of each agent was ranked 1-5 in each of the following in vitro assays: 1) inhibition of [3H]histamine binding to microsomal HIC, 2) inhibition of histamine binding to microsomal P450, 3) inhibition of the P450-catalyzed demethylation of aminopyrine, 4) inhibition of lymphocyte mitogenesis, and 5) stimulation of tumor colony formation. An overall rank score was assigned to each drug and correlated with tumor growth stimulation in vivo. Two laboratories conducted in vivo studies in a blinded fashion. Female C57BL and C3H mice were given a subcutaneous injection on day 1 of syngeneic B16F10 melanoma cells (5 x 10(5)) or C-3 fibrosarcoma cells (1 x 10(5)), respectively. Mice were randomly assigned to treatment groups, then received a single, daily intraperitoneal injection of an estimated human-equivalent dose (or range of doses) of antihistamine or vehicle control for 18-21 days before being killed. Tumors were surgically removed and wet weights compared statistically among groups. RESULTS: The cumulative potency of each drug in affecting tumor growth or growth mechanisms in the five in vitro assays ranked as follows: Loratidine and astemizole ranked highest and were equally potent, followed in decreasing order by hydroxyzine, doxylamine, and cetirizine. A significant correlation (r = .97; P < .02) was observed between the rank order of potency of the antihistamines in all five in vitro assays and the rank order to enhance tumor growth in vivo: Loratidine and astemizole significantly (P < .001) promoted the growth of both melanoma and fibrosarcoma, hydroxyzine significantly (P < .001) promoted the growth of melanoma, while doxylamine and cetirizine did not promote the growth of either tumor. CONCLUSION: Data demonstrate that the in vitro assays predicted the propensity of each H1-antihistamine to stimulate cancer growth in vivo. IMPLICATION: These in vitro tests may prove valuable to screen potential tumor growth promoters.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7909571&dopt=Abstract
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Br J Dermatol. 1994 Jul;131(1):78-84.
Characterization and analysis of skin wealing by computerized non-linear regression.
Sharpe GR, Shuster S.
Dermatology Unit, University of Liverpool, U.K.
Weal formation in human skin may be induced by histamine, histamine releasers and other inflammatory mediators. Weals occur spontaneously in chronic urticaria, and in response to frictional pressure in dermographic urticaria. We present an improved method for the analysis of wealing in human skin by the use of non-linear regression. The method has the advantage of speed, and by the use of non-linear regression permits the full characterization of the response curves. The time course of histamine-induced wealing is a double exponential function corresponding to the separate components of weal appearance and disappearance. Dermographic wealing corresponds to an increasing exponential function with increasing pressure. The method of computerized non-linear regression is a considerable advance on previous methods for the analysis of urticarial wealing, the effect of vasoactive agents, and their therapeutic action.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8043424&dopt=Abstract
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A high-performance liquid chromatographic method for the quantitation of cetirizine in human plasma is presented. The method is based on liquid-liquid extraction with dichloromethane and reversed-phase chromatography with spectrophotometric detection at 232 nm. Gradient elution was used to remove late eluting peaks. Diazepam was used as the internal standard. The limit of quantitation was 10 ng/ml using 0.5 ml of plasma. Within-day and between-day precision expressed by relative standard deviation was less than 10% and inaccuracy did not exceed 8%. The assay was applied to the analysis of samples from a pharmacokinetic study.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10677003&dopt=Abstract
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