Pharmacological tests

In the search for new structures with antiinflammatory activities some 1-substituted 3-dimethylaminoalkoxy-lJ/-indazoles (704) have been synthesized and pharmacologically tested (66JMC38). Doses of 20-40 mg g i.p. produced sedation, muscle relaxation and motor incoordination, whereas doses of 80-100 mg kg produced depression. Toxicity was fairly constant in all series, varying from 120 to 150 mg kg i.p., with the exception of compounds possessing a nitro group or an amino group in the indazole nucleus, which provoked cyanosis. 

According to-Vellard, a Strychnos sp. similar to S. medeola is used by the Nambikwaras. Brasil, Campos and Kuhlmann have mentioned three S. American species of Strychnos, viz., S. diplinerva, S. off. albiflora Prog and S. brevifolia A.D.C., in which, using extracts of the roots in comparison with Tecuna curare, they have found curarising activity by pharmacological tests in rabbits. 

It has long been known that quaternary ammonium salts can exert a curare-like action, and in recent years much attention has been given to the synthesis and pharmacological testing of such products work on this subject up to 1936 has been reviewed by Ing, and more recently a theoretical discussion of the relationship between structure and action in drugs of this type has been provided by Holmes, Jenden and Taylor.Chase, Lehmann and Yonkmann have compared the action of quaternary salts of quinine with that of -erythroidine hydrochloride and of dihydro- -erythroidine hydrobromide. Quinine ethochloride shows marked curariform action of short duration. ... 

Non-Clinical Study Reports Toxicological and Pharmacological Tests 111... 

Physicochemical and biological parameters obtained from 6 oxazepine (X = O) and 6 thiazepine (X = S) neuroleptics. These include Hammett s electronic parameter (o ), lipophilicity (log P) and its squared value, and the activities (log l/EDjn) in two pharmacological tests in rats [41]. 

The biplots show which binding tests are predictive for which pharmacological tests. Binding to the haloperidol and apomorphine labeled receptors corresponds with inhibition of agitation and stereotypy in rats, binding to the spiperone receptor... 

In the discovery phase, a reaction route is developed to allow synthesis of a maximum number of analogues for pharmacological testing. Since the focus is on synthetic flexibility, issues of scale are not central. Once a lead compound exhibits a useful pharmacological activity and is identified as a candidate for further development, larger scale synthesis is required to evaluate stability, bioavailability, toxicity, physicochemical properties, and other compound properties. The Chemical Development Department is usually involved in the preparation of supplies for these activities. 

For aerosols of nonvolatile liquid and powdery compounds, the concentration of the mist or dust atmosphere must be expressed in terms of milligrams per liter or milligrams per cubic meter (mg/m3) of air. With advances in biotechnology, many pharmacological testing techniques are based on specific receptor bindings, in which the ratio of the number of molecules to those of the receptors are considered, in... 

The use of closely inbred animals in pharmacological testing tends, of course, to lessen observed variability. 

Predictive Value of Non-Clinical Safety Pharmacology Testing to Humans. .270... 

In this section, a brief summary of the nature, frequency, and consequences of adverse drug reactions (ADRs) in two clinical situations is presented. There are ADRs experienced by healthy volunteers and patients participating in clinical studies with potential new medicines and those experienced by patients who are prescribed licensed medicines. A review of these two situations points to areas of success with the current practices for non-clinical safety pharmacology testing but also identifies some areas where further research might lead to new or better safety pharmacology tests. Prior to reviewing the literature, some... 

Regulatory guidance for non-clinical cardiovascular safety pharmacology testing is given in the ICH S7A and B.25,42 The effects of an NCE on blood pressure, heart rate, and the ECG should be evaluated. Furthermore, in vivo, in vitro, and ex vivo evaluations, including methods for (assessing) repolarization and conductance abnormalities, should... 

Galanakis D, Ganellin CR, Malik S, Dunn PM. Synthesis and pharmacological testing of dequalinium analogues as blockers of the apamin-sensitive Ca (2+)-activated K+ channel variation of the length of the alkylene chain. J Med Chem 1996 39 3592-3595. 

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