Molecular pharmacological studies

A special problem arose with respect to the antiplasmodial drugs chloroquine (Resochin) and quinacrine (Atebrin). Plasmodia can not be propagated in cell-free lifeless media and the limited availability of erythrocytic plasmodial cultures severely limits biochemical or molecular pharmacological studies on the action of antimalarials. The actions of chloroquine and quinacrine were, therefore, studied in Bacillus megaterium or E. coli, respectively 22 ... 

Molecular Pharmacology. Molecular pharmacology studies the chemical and physical properties of drugs to define how they interact with receptors at the molecular level. This field is deeply rooted in mathematical techniques and molecular biology. Molecular pharmacology deals with all classes of drugs and aU types of receptors at the cellular and subcel-lular level. 

Z, ] McClarin, T Klein and R Langridge 1985. A Quantitative Structure-Activity Relationship and ecular Graphics Study of Carbonic Anhydrase Inhibitors. Molecular Pharmacology 27 493-498. 

Figure 3 The chemical structures of the ligands used in the molecular modeling study of the Di dopamine receptor. The ligands were divided into two groups (active and inactive) based on their pharmacological properties. The hypothesized pharmacophoric elements are shown in bold.

Iwamoto T (2004) Forefront of Na+/Ca2+ exchanger studies molecular pharmacology of Na+/Ca2+ exchange inhibitors. J Pharmacol Sci 96 27-32... 

EARLY PHARMACOLOGICAL STUDIES AND THE IMPACT OF MOLECULAR GENETIC TECHNIQUES... 

In recent years it has been realized that molecular modeling studies of the alkaloidal molecules having different pharmacological activities are highly important in order to explain their mechanisms, at least partially in some cases. This chapter presents and critically reviews some examples of molecular modeling studies of alkaloids, based on their different biological properties or sometimes performed in parallel to explain their biochemical effects. 

Paluchowska et al. (2002) reported the synthesis, pharmacological studies, and conformational analysis utilizing classical molecular modeling approaches of some arylpiperazine or 1,2,3,4-tetrahydroisoquinoline derivatives of the known and flexible 5-HT ia receptor ligands with different intrinsic activities at nanomolar levels [63]. The SAR is shown in Table 4. The synthetic steps involved for some of the compounds mentioned in Table 4 are shown in Scheme 2 [63]. 

Pharmacological studies and clinical applications of individual Gelsemium alkaloids or of the total alkaloids have never been reviewed before, so a preliminary treatment is presented in this chapter based on the limited data collected so far. For the convenience of identification, the names, molecular formulas, sources, as well as main references of all the Gelsemium alkaloids reported in the literature to date are listed in Table I. 

These initial studies suggested that the posterior hypothalamus may contain a wakefulness center and provided the initial impetus to pursue further research to understand the role of HA and the posterior hypothalamus in sleep-wakefulness. The next cycle of research substantiating the role of HA in sleep-wakefulness consisted mainly of electrophysiological, biochemical/molecular, and pharmacological studies. 

Blake AD, Bot G, Reisine T. Molecular pharmacology of the opioid receptors. In Molecular Neurobiology of Pain. Progress in Pain Research and Management, Vol. 9 (Borsook D, ed), International Association for the Study of Pain Press, USA, 1997 259-273. 

Sayre, R., Harlos, J. P., Rein, R., in Molecular orbital studies in chemical pharmacology (L. B. Kier, ed.), pp. 207—237, Springer-Verlag New York, Inc. Berlin-Heidelberg-New York Springer 1970. 

In order to fully exploit the information contained in the X-ray structures, interdisciplinary research is required, involving such disciplines as computational chemistry, medicinal chemistry, and molecular pharmacology in partnership with X-ray crystallography. In this context, the X-ray structures provide an excellent springboard for studying structure-activity/selectivity relationships, as well as the structure-based design of new ligands. 

Green, J. P., and Kang, S. (1970) The correlation of electronic structures of indole derivatives with their biological activities. In Molecular Orbital Studies in Chemical Pharmacology, edited by L. B. Kier, pp. 105-120. Springer-Verlag, New York. 

Palacios, J. M. (1983) Quantitative receptor autoradiography Application to the study of multiple serotonin receptors in rat cortex. In CNS Receptors—From Molecular Pharmacology to Behaviour, edited by P. Mandel and F. V. de Feudis. Raven Press, New York. Adv. Biochem. Psychopharmacol., 37 455-463. 

The maintenance of desired phenotypic features over multiple generations will need to be periodically evaluated. If a feature is unstable over the experimental period, it will be necessary to evaluate other clones or generate new clones. If the phenotype changes as a result of multiple subcultures, earlier passages can be thawed (if they have been appropriately generated and stored) and utilized appropriately. Once the immortalized clones have been established and characterized for desired phenotypic features, they can then be used for numerous biochemical, molecular biological, and pharmacological studies. 

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