Data pharmacology

Care should be exercised when attempting to interpret in vivo pharmacological data in terms of specific chemical—biological interactions for a series of asymmetric compounds, particularly when this interaction is the only parameter considered in the analysis (10). It is important to recognize that the observed difference in activity between optical antipodes is not simply a result of the association of the compound with an enzyme or receptor target. Enantiomers differ in absorption rates across membranes, especially where active transport mechanisms are involved (11). They bind with different affinities to plasma proteins (12) and undergo alternative metaboHc and detoxification processes (13). This ultimately leads to one enantiomer being more available to produce a therapeutic effect. 

In addition, sources of pharmacological data and comparative information on trade names used in various countries were obtainad from ... 

Ideally, pharmacological data should directly be fit to specific models and parameters derived from the direct fit. However, there are cases where the specific models predict surrogate parameters that can be derived without fitting data to the specific model. This can be an advantage. For example, the equation for simple competitive antagonism of receptors (see Section 6.3) is... 

There are practical guidelines that can be useful for fitting pharmacological data to curves. 

Wientjes MG, Badalament RA, An JL. Use of pharmacologic data and computer simulations to design an efficacy trial of intravesical mitomycin C therapy for superficial bladder cancer. Cancer Chemother Pharmacol 1993,32(4) 255-62. 

Fig. 37.6. PLS biplot obtained from the pharmacological data in Table 37.9, after log double-centering and analysis by two-block PLS [56]. Circles represent 17 reference neuroleptic compounds, squares denote tests. Areas of circles and squares are proportional to the potencies of the compounds and the sensitivities of the tests, respectively. Reproduced with permission of E.J. Kaijalainen.

CSline. CSline [84] provides information on well-designed and well-executed clinical trials of drugs currently under study or in use in humans. This information includes study objectives, design, population, intervention groups, withdrawals, adverse reactions, endpoints and results, conclusions, and references. The CSline database covers more than 500 drugs currently on the market or in development. Pharmacological data from more than 2000 journal articles, congresses, and books are added each year. The product is commercially available on CD-ROM from Prous Science and is updated every 2 months. 

Several patent applications claiming a class of inhibitors derived from the DA transporter (DAT) inhibitor methylphenidate (12) have been published [48-50], A variety of structural modifications represented by analogs 13-15 have been claimed and pharmacological data has been reported for analog SSR-504734 (13) [51-53]. 

Other patent applications for scaffolds derived from methylphenidate have been published (16-18) however, no pharmacological data has been reported [57-59]. 

There is a plethora of in vitro and in vivo pharmacological data with MOR-selective agonist and antagonists implicating MOR in the disruption of GI function by opioid analgesics [2,9]. This pharmacology is consistent with... 

Van de Velde P, Nique F, Planchon P, Prevost G, Bremaud J, Hameau MC, Magnien V, Philibert D, Teutsch G (1996) RU 58668 further in vitro and in vivo pharmacological data related to its antitumoral activity. J Steroid BioChem Mol Biol 59 449-457... 

European Union. The standard European Union toxicology and pharmacologic data requirements for a pharmaceutical include... 

By making use of both the electrophilic reactivity (Elumo) and ad hoc shape (Vdlf) descriptors, the following equation was obtained, which accounts for about 77% of the variance in the pharmacological data. 

West, Clarence J. "Pharmacological Data", Chemical Warfare Monograph No. 50, Chemical Warfare Service, Edgewood Arsenal Technical Library. 

Mode-of-Action Hypotheses. May we now turn to consider some of the suggested mechanisms put forward to explain the hypotensive action of the 3-blocking drugs and see if any are compatible with the clinical and pharmacological data. Before doing so however, it perhaps would be useful to summarise the characteristics of the anti-hypertensive action of the drugs. 

DrugMatrix Iconix Pharmaceuticals, Inc. [http // www.iconixpharma.com/] Pharmacology data integrated with extensive gene expression data... 

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