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Physicochemical, quantum chemical, and other theoretical studies of the mechanism of action of cns agents: Anesthetics, narcotics and narcotic antagonists, and psychotropic drugs
Author(s) -
Kaufman Joyce J.,
Koski Walter S.
Publication year - 2009
Publication title -
international journal of quantum chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.484
H-Index - 105
eISSN - 1097-461X
pISSN - 0020-7608
DOI - 10.1002/qua.560090705
Subject(s) - chemistry , quantum chemical , lipophilicity , partition coefficient , computational chemistry , van der waals force , molecule , stereochemistry , organic chemistry
Pharmacological effectivity of CNS agents is governed both by lipophilicity and by topographical and electronic structure of pharmacophores. Three different classes of drugs investigated (anesthetics, narcotics and narcotic antagonists, and psychotropic drugs) depend differently on these various factors. Isonarcotic pressures of most anesthetics are proportional to √a (the van der Waals' constant). This has been verified by theoretical thermodynamicl derivation. Narcotic and narcotic antagonist effectivities are governed both by their lipophilicities and by electronic and topographical properties. pK a 's, partition coefficients, and drug distribution coefficients of these drugs have been measured accurately by a micro‐titrimetric titration technique as a smooth function of pH and these results have been related to their clinical significance. Calculated quantum chemical electron densities and molecular orbital energies have been verified by experimental esca and pes measurements. Neuroleptics require not only high partition coefficients but also very specific topography. Quantum chemical calculations on a hitherto unknown series indicate that these should be effective neuroleptics; this was confirmed by subsequent report of their synthesis and testing.