In order to determine the structural requirements that are important for GABA binding affinity, a quantum-chemical-based conformational study has been B performed, followed by a similarity analysis which includes 12 GABA analogs. Due B w Ž . to the flexibility of the structures, a semigrid GABA analog 2RS-5,5-dimethyl B x morpholinyl-acetic acid has been used as a template for the amonium moiety in order to help to identify the active conformation. Both in vacuo, and solvent-simulated calculations, for the physiological media modeled as water molecules, have been compared, for this Ž Ž . . Ž . analog, at ab initio G94, 6-31 q G d,p and semiempirical PM3 levels, respectively. On the basis of this comparison, the results of in vacuo PM3 calculations have been chosen for the similarity analysis. We have included, in the calculations, a group of molecules heterogeneous enough to become representative of the different families that can bind to the GABA receptor site. Following their comparison we report the leading characteristics B that can be related to their binding capability and define a pharmacophoric pattern for GABA analogs. The latter is compared with the one previously found for the binding B affinity at the GABA receptor site.