(a) Orthogonal views of the overlap (yellow) volumes of α1β3γ2 (red) and α2β3γ2 (green)
(b) Orthogonal views of the overlap (yellow) volumes of α2β3γ2 (red) and α3β3γ2 (green)
(c) Orthogonal views of the overlap (yellow) volumes of α4β3γ2 (red) and α6β3γ2 (green)
(d) Orthogonal views of the overlap (yellow) volumes of α1β3γ2 (red) and α6β3γ2 (green)
(e) Orthogonal views of the overlap (yellow) volumes of α5β3γ2 (red) and α1β3γ2 (green)
(f) Diazepam and the unified pharmacophore descriptors
Figure 48: The previous benzodiazepine subtype selective receptor pharmacophore models [23]. (1) The region in the α5 subtype is larger than the α1 subtypes. This is a key result. It is the principle difference between α5 subtypes compared to α2 and α3 subtypes, but especially in regard to α1 subtypes ( smaller in α1). (2) The region is larger in the α5 subtype as compared to the α1, α2, α3, α4, and α6 BzR sites. R analogs of benzodiazepines with pendant phenyls had increased affinity to α5 supporting the larger pocket in this receptor subtype, while S isomers bound to α2, α3, and α5 subtypes because of different conformational constraints.