By E. W. McChesney, C. D. Fitch (auth.), Wallace Peters M.D., DSc, FRCP, DTM & H, William H. G. Richards BSc, Ph. D. (eds.)
The development of this quantity has been guided through own convictions. event within the box of experimental chemotherapy, either within the pharmaceutical and academia, has confident us that contemporary quantum technological advances in biochemistry, molecular biology, and immunology will allow and, certainly, necessitate an more and more higher use of rational drug improvement sooner or later than has been the customized in past times. partially l, accordingly, we requested our members to supply targeted studies masking the biology of the malaria parasites and their relation with their hosts, the experimental approaches together with tradition ideas which are essential to take a drug from fundamental screening to medical trial, and an account of antimalarial drug resistance. Our moment conviction is that many learn employees are all too loath to benefit from the teachings of the prior. consequently we requested the individuals to half 2 of this quantity to study very completely the commonly scattered yet voluminous literature on these few chemical teams that experience supplied the antimalarial medicines in scientific use this day. a lot will be realized from the background in their improvement and the issues that experience arisen with them in guy. a few certainly should still have a lot to provide in the event that they should be deployed in greater methods than they're at the present. this question has been taken up by way of a number of authors.
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Extra info for Antimalarial Drug II: Current Antimalarial and New Drug Developments
MCCHESNEY and C. D. FITCH of the drug to melanin is clearly the critical factor in determining the wide divergence in response of the two strains (SAMS and EpSTEIN, 1965). (}) Other Tissues. In a few cases tissues or organs other than any of those mentioned above have been studied. COllEN et al. (1963), for example, found evidence, in auto radiograms of rats prepared following the injection of [14c]CQ, of considerable accumulations in salivary gland, thymus, hypophysis and frontal sinus. Pituitary gland does not appear to have been studied otherwise as a repository for CQ in the rat, but its strong affinity for the drug has been demonstrated in the rhesus monkey (see Table 3, line 18).
Since presumably little, if any, of the unchanged drug would remain in the organism at this time, the results would not be at all comparable to those obtained for CQ in the same species. P) Dogs. Results are given for one animal in Table 4, line 25, and for another in Table 5, line 12. Again, rapid metabolism (see Sect. II, below) complicates interpretation of the data, in comparison to those obtained for other members of the 4-aminoquinoline series, but it probably does account for the low observed tissue concentrations.
Deposition of CQ in the pigment epithelium, specifically, was demonstrated by the development of characteristic fluorescence in this layer. DALE et al. (1965) attempted to produce a condition comparable to human retinopathy by giving considerably higher daily oral doses of CQ (25 mg/kg; ten times the usual human anti-RA dose) to albino and pigmented rabbits. They also reported no data for CQ concentrations in various parts of the eye, but they did find characteristic pigmentary deposits in the choroid, pigmented epithelium, iris and ciliary body of the pigmented animals only.
Antimalarial Drug II: Current Antimalarial and New Drug Developments by E. W. McChesney, C. D. Fitch (auth.), Wallace Peters M.D., DSc, FRCP, DTM & H, William H. G. Richards BSc, Ph. D. (eds.)