Drugs activity profiles

CmC, a preservative in commercial preparations of some intravenous drugs, activates CICR in a way similar to that of caffeine. 4-CmC is more potent than caffeine and shows isoform-dependent activation profiles it is much less effective in RyR3 than RyRl or RyR2. 

Figure 17.9 Schematic representation of the proposed activity profile of an ideal neuroleptic. The figure shows DA pathways to the prefrontal cortex, mesolimbic nucleus accumbens and striatum the effects required for an ideal drug on the DA influence and symptoms there and to what extent they are met by most typical and atypical neuroleptics and by clozapine. Note that while all atypical neuroleptics induce few extrapyramidal w side-effects (EPSs) few of them, apart from clozapine, have much beneficial effect in overcoming negative symptoms of schizophrenia ...

Suomalainen, P., Johans, G., Soderlund, T., Kinnunen, P. K. Surface activity profiling of drugs applied to the prediction of blood-brain barrier permeability. J. Med. Chem. 2004, 47, 1783-1788. 

P. J. Lewi, Spectral mapping, a technique for classifying biological activity profiles of chemical compounds. Arzneim. Forsch. (Drug Res.), 26 (1976) 1295-1300. 

Loeomotor aetivity has historically been used as an index of psychostimulant effects. Simple assessment of amount of loeomotor activity can provide the basis for anatomical as well as pharmaeologieal analysis of the neural substrates that mediate the behavioral expression of stimulant action. More sophisticated behavioral measurement systems ean reeord multiple measures of activity and describe spatial and temporal patterning of loeomo-tion. In such systems, qualitative aspects of behavioral activation can be evaluated by examining the entire activity profile. A comparison of the effects of novel drugs with those produced by well-characterized substanees may lead to a better understanding of their mechanisms of action and subjective properties. 

Drug-specific considerations in antimicrobial selection include the spectrum of activity, effects on nontargeted microbial flora, appropriate dose, pharmacokinetic and pharmacodynamic properties, adverse-effect and drug-interaction profile, and cost. 

In order to produce an adequate tablet formulation, certain requirements, such as sufficient mechanical strength and desired drug release profile, must be met. At times this may be a difficult task for the formulator to achieve, due to poor flow and compactibility characteristics of the powdered drug. This is of particular importance when one only has a small amount of active material to work with and cannot afford to make use of trial-and-error methods. The study of the physics of tablet compaction through the use of instrumented tableting machines (ITMs) enables the formulator to systematically evaluate his formula and make any necessary changes. 

This chapter provides an introduction to the pharmaceutical sector, and the business of developing new active pharmaceutical ingredients (API). Crystallization is the preferred method of isolating commercial API products because it offers a highly efficient means of purification. The crystallization process is also where the physical properties of the drug substance are defined. These properties can have a significant impact on the formulated product and process, and eventually on the drug release profile in the patient. 

While this may in fact be the case for natural product mixtures, it is rarely the case when dealing with synthesized mixtures. Despite our attempts to create real molecular diversity in the test tube, our efforts have not even begun to anticipate the true diversity of atomic connectivity within "drug space" (estimated to be of the order of 1063 unique compounds, theory, famously in this case, greatly outpacing the amount of matter in the universe). Thus, combinatorial chemistry was never practically able to produce true chemical diversity and compounds produced in such library format ended up looking very much like one another, with the attendant similarities in biological activity profiles. 

Prior to formulating a drug substance into a dosage form, the desired product type must be detemined for planning the product formulation activities. Then, various initial formulations are developed and then evaluated for selected parameters, such as drug-release profile, bioavailability, clinical effectiveness, and for any scale-up problems. The best formulation is selected and becomes the master formula. Each batch of the product subsequently prepared must meet the specifications established in this master formula. 

Activity profiles predicted by a robust method such as the GNB can be used, for example, to make in vitro/in vivo correlations, and thus anticipate adverse drug effects of lead candidates in drug development. 

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