Biochemical pharmacology

Vinblastine, vincristine, and structurally related analogs inhibit microtubule polymerization by 50% at concentrations in the range 0.1-1 xM, and the process of tubulin addition to preformed microtubules, at steady state, is comparably sensitive to inhibition by these agents (5). As shown in Table I, the differences in values for inhibition of steady-state tubulin addition by vinblastine, vincristine, vindesine, and vinepidine were relatively small, but the pattern of activity in the tubulin addition system did not parallel that observed when the compounds were evaluated for effects on the proliferation of B16 melanoma cells in vitro. Vinepidine was more than twice as potent as vinblastine as an inhibitor of steady-state tubulin addition but nearly 10-fold less potent than vinblastine as an inhibitor of cell growth (i). 

Inhibition of Tubulin Addition and Cell Proliferation bt Vinblastine and Related Compounds 

Earlier studies indicated that vinblastine binding to tubulin dimers involves interaction of two molecules of vinblastine with each dimeric pro- 

A wide variety of other biochemical effects has been reported to be associated with treatment of cells with vinblastine, vincristine, and related compounds (S). These effects include inhibition of the biosynthesis of proteins and nucleic acids and of aspects of lipid metabolism it is not clear whether such effects contribute to the therapeutic or toxic actions of vincristine and vinblastine. Vinblastine and vincristine inhibit protein kinase C, an enzyme system that modulates cell growth and differentiation (9). The pharmacological significance of such inhibition has not been established, however, and it must be emphasized that the concentrations of the drugs required to inhibit protein kinase C are several orders of magnitude higher than those required to alter tubulin polymerization phenomena (10). 

Vincristine and vinblastine are generally considered to act specifically on the metaphase portion of the mitotic (M) stage of the cell cycle as a consequence of perturbations of the structure and function of tubulin. A characteristic action of the drugs is production of mitotic arrest in which the tJercentage of cells in mitosis in a given population of cells will rise from a few percent to 50% and more after treatment with a drug such as vinblastine. There are reports, however, that these drugs can interfere with other phases of the cell cycle in ways not clearly related to interference with tubulin function (5). 

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S-Acetylthiocholine iodide [1866-15-5] M 289.2, m 203-204°, 204°, 204-205°. Recrystd from propan-l-ol (or wo-PrOH, or EtOH/Et20) until almost colourless and dried in a vacuum desiccator over P2O5. Solubility in H2O is 1% w/v. A 0.075M (21.7mg/mL) solution in O.IM phosphate buffer pH 8.0 is stable for 10-15 days if kept refrigerated. Store away from light. It is available as a 1% soln in H2O. [Biochemical Pharmacology 7, 88 I96I IR Hansen Acta Chem Scand 13 151 1959, 11 537 1957 Clin Chim Acta 2 316 7957 Zh Obshch Khim 22 267 1952.]... 

The anxiolytic agent buspirone (131) is notable for the fact that it does not interact with the receptor for the benzodiazepines. This difference in biochemical pharmacology is reflected in the fact that buspirone (131) seems to be devoid of some of the characteristic benzodiazepine side effects. The spiran function is apparently not required for anxiolytic activity. Alkylation of 3,3-dimethylglutarimide with dichlorobutane in the presence of strong base yields the intermedi-... 

Laboratory of Biochemical Pharmacology Emory University/Veterans Affairs Medical Center,... 

L.C. Bassit Laboratory of Biochemical Pharmacology, Center for AIDS Research, Emory University School of Medicine/Veterans Affairs Medical Center, Atlanta,... 

Chipman, J.K. and Walker, C.H. (1979). The metabolism of dieldrin and two of its analogues the relationship between rates of microsomal metabolism and rates of excretion of metabolites in the male rat. Biochemal Pharmacology 28, 1337-1345. 

Maggs, J.L., Grabowski, P.S., and Park, B.K. (1983). Drug protein conjugates. 2. An investigation of the irreversible binding and metabolism of 17-alpha-ethinyl estradiol in vivo. Biochemical Pharmacology 32, 301-308. 

Rosenberg, D.W. and Drummond, G.S. (1983). Direct in vitro effects of TBTO on hepatic cytochrome P450. Biochemical Pharmacology 32, 3823-3829. 

MIDDLETON E J and KANDASHWAMi c (1992) Effects of flavonoids on immune and inflammatory cell function. Biochemical Pharmacology 43, 1167-79. 

HAGIWARA M, INOUE s, TANAKA T, NUNOKI K, ITO M and HiDAKA H (1988) Differen-tial effects of flavonoids as inhibitors of tyrosine protein kinases and serine/threonine protein kinases Biochemical Pharmacology 37, 2987-92. 

Relationship between flavonoid structure and inhibition of phos-phatidylinositol 3-kinase a comparison with tyrosine kinase and protein kinase C inhibition Biochemical Pharmacology 53, 1649-57. 

Roberts, J. and Shaw, C.F. Ill (1998) Inhibition of erythrocyte selenium-glutathione peroxidase by auranofin analogs and metabolites. Biochemical Pharmacology, 55, 1291-1299. 

Snyder, R.M., Mirabelli, C. and Crooke, S.J. (1986) Cellular association, intracellular distribution, and efflux of auranofin via sequential ligand exchange reactions. Biochemical Pharmacology, 35, 923-932. 

Shaw, C.F. Ill, Isab, A.A., Coffer, M.T and Mirabelli, C.K. (1990) Gold(I) efflux from auranofln-treated red blood cells. Evidence for a glutathione-gold-albumin metabolite. Biochemical Pharmacology, 40, 1227-1234. 

Jacoby, W.B. (1980) The Enzymatic Basis of Detoxication, Volumes J and II. Biochemical Pharmacology and Toxicology Monograph Series. Academic Press, New York. 

These data clearly illustrate the enantioselectivity of the (-l-)-isomers of MDA, MDMA, and MBDB in producing an MDMA-like stimulus and underscore the fact that in vitro studies of the biochemical pharmacology of these substances should reveal similar selectivity, once the primary pharmacological process underlying the interoceptive cue is identified. The data also indicate that (-l-)-MDA is the most potent of all the drugs tested in MDMA- or in (-t)-MBDB-trained animals. The faet that (-l-)-MDA does not substitute in amphetamine-trained animals in our studies supports the argument that the pharmacology of this enantiomer of MDA is MDMA-like and is not like amphetamine. 

When a particular behavioral pharmacology is associated with a specific biochemical action within a series of congeners, it is likely that the biochemistry is a functional component of the observed behavioral activity. This is not necessarily the case if only one or a few molecules are available for study they may well possess ancillary biochemical pharmacology that is... 

Figure 7.46 Fluorescence quenching of doxorubicin by DNA [597] (a) doxorubicin in aqueous solution, quenched immediately on addition of DNA (b) doxorubicin fluorescence not affected by vesicles (c) Doxorubicin preequihbrated with vesicles, and then subjected to DNA. The fraction bound to the outer membrane leaflet is immediately quenched by the DNA. (d) Same as (c), but multilamellar vesicles used. The left arrow represents a 5-min interval and applies to the first three cases the right arrow represents 30-min interval and applies to (d) only. [Reprinted from Ronit Regev and Gera D. Eylan, Biochemical Pharmacology, vol. 54, 1997, pp. 1151-1158. With permission from Elsevier Science.]...

Zoltoski, R. K Cabeza, R. J. 8r Gillin, J. C. (1999). Biochemical pharmacology of sleep. In Sleep Disorders Medicine Basic Sciences, Technical Considerations and Clinical Aspects, ed. S. Chokroverty and R. B. Daroff, 2nd edn, pp. 63-94. Boston, MA ... 

Illes P (1989). Modulation of transmitter and hormone release by multiple neuronal opioid receptors. Review of Physiological and Biochemical Pharmacology, 112, 139-233. 

Hamza, M., Lloveras,J., Ribbes, G., Soula, G. and Douste-Blazy, L. (1983) An in vitro study of hemicholinium-3 on phospholipid metabolism of Krebs II ascites cells. Biochemical Pharmacology 32, 1893—1897. 

Kinesins mediate anterograde transport in a variety of organisms and tissues. Since its discovery, much has been learned about the biochemical, pharmacological and molecular properties of kinesin [44, 45], Kinesin is the most abundant member of the kinesin family in vertebrates and is widely distributed in neuronal and nonneuronal cells. The holoenzyme is a heterotetramer comprising two heavy chains (115-130 kDa) and two light... 

Freedman, D. X., and Boggan, W. O. (1981) Biochemical pharmacology of psychotomimetics. In Handbook of Experimental Pharmacology, edited by F. Hoffmeister and G. Stille, pp. 57-88. Springer-Verlag, Berlin. 

Bellemann, P. (1980). Primary monolayer culture of liver parenchymal cells and kidney cortical tubules as a useful new model for biochemical pharmacology and experimental toxicology. Studies in vitro on hepatic membrane transport, induction of liver enzymes, and adaptive changes in renal cortical enzymes. Arch. Toxicol. 44 63-84. 

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