H. Van De Waterbeemd

Similarities of pharmacophoric patterns revealed by the MEP of metoclopramide, molindone and piquindone, a subgroup of dopamine D-2 receptor antagonists

Abstract Molecular electrostatic potential (MEP) calculations based on ab initio wave functions have been used to compare three compounds belonging to two distinct chemical series (substituted benzamides (metoclopramide) and indolones (piquindone and molindone)). These compounds have highly similar pharmacological properties at the receptor level (antagonists binding selectively to the dopamine D2 receptor and in a sodium-dependent manner). The MEPs of these compounds show close similarities and form a common pharmacophoric pattern.

The influence of aromatic substituents on the binding of substituted benzamides to dopamine D-2 receptors: congruent QSAR and MEP analyses

tes of MTX and anti-tumour monoclonal antibodies

The thermodynamics of agonist and antagonist binding to dopamine D-2 receptors.

ddwin et a1 1986). Overall, these and other related studies (Corvalan et d 1987) indicate that modification of drug biodistribudon with monoclonal antibodies and/or tissue specific targeting with complexes formed with hybrid antibodies may be valid approaches to prolongation of drug survival and/or site-specific targeting. The degree of drug loading of monoclonal antibodies, with theoretical of two molecules per molecule with anti-drug antibody and one molecule per molecule of hybrid antibody, might be a limitation, since the amount of antibody required to carry conventional therapeutic doses of drug would be very high. In addition the extent ofextravasation of antibody is much smaller than that of drugs. But, as this study shows, the survival of drug is markedly prolonged simply with the anti-drug antibody, and the additional site targeting effect possible with hybrid antibodies might mean the possible use of greatly reduced doses of drug.