By Gert Fricker, Melanie Ott, Anne Mahringer
Medicinal chemistry is either technological know-how and paintings. The technology of medicinal chemistry bargains mankind one in every of its top hopes for bettering the standard of existence. The artwork of medicinal chemistry keeps to problem its practitioners with the necessity for either instinct and adventure to find new medicines. consequently sharing the event of drug study is uniquely valuable to the sphere of medicinal chemistry. Drug study calls for interdisciplinary team-work on the interface among chemistry, biology and drugs. consequently, the topic-related sequence subject matters in Medicinal Chemistry covers all appropriate facets of drug study, e.g. pathobiochemistry of ailments, identity and validation of (emerging) drug goals, structural biology, drugability of goals, drug layout techniques, chemogenomics, artificial chemistry together with combinatorial equipment, bioorganic chemistry, average compounds, high-throughput screening, pharmacological in vitro and in vivo investigations, drug-receptor interactions at the molecular point, structure-activity relationships, drug absorption, distribution, metabolism, removal, toxicology and pharmacogenomics. in most cases, particular volumes are edited via renowned visitor editors.
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Additional info for The Blood Brain Barrier (BBB)
Sample text
Brain Res Brain Res Rev 25:27–49 63. de Lange EC, de Boer AG, Breimer DD (2000) Methodological issues in microdialysis sampling for pharmacokinetic studies. Adv Drug Deliv Rev 45:125–148 64. Sawchuk RJ, Elmquist WF (2000) Microdialysis in the study of drug transporters in the CNS. Adv Drug Deliv Rev 45:295–307 65. de Lange EC, Ravenstijn PG, Groenendaal D, van Steeg TJ (2005) Toward the prediction of CNS drug-effect profiles in physiological and pathological conditions using microdialysis and mechanism-based pharmacokinetic-pharmacodynamic modeling.
A combinatorial map of Kp,uu,brain can be made using Kp,brain determined as above, and Vu,brain (or fu,brain) and fu,plasma measurements [34]. Equation (14), or a modification that includes 1/Vu,brain instead of fu,brain (Eq. (20)), can then be used to calculate Kp,uu,brain. Kp,uu,brain can also be determined using microdialysis [36]; however, the time needed for this method and the lack of its success with many lipophilic compounds mean that microdialysis is less feasible in a drug discovery setting.
In vivo recovery estimations are needed for quantitative studies when mapping the extracellular environment and BBB transport of drugs. Measurement of in vitro recovery can never adequately replace in vivo estimations, as the tissue surrounding the probe significantly influences the exchange across the probe membrane. These peri-probe processes include the exchange between extracellular sites and the vasculature, where active efflux transporters like P-gp have a substantial influence on the recovery, as well as the diffusion and metabolism, of the compound within the tissue [62].