Possible use of non-neuroleptic isomers of anti-psychotics in anti-sickling therapy.

Non-neuroleptic isomers and derivatives of three types of anti-psychotic drugs (phenothiazine, thioxanthene and benzocycloheptapyridoisoquinoline) were found to have in vitro anti-sickling activity. The anti-sickling activity of non-neuroleptic isomers is of the same magnitude as that of the anti-psychotic forms. The degree of the suppression of sickling ranged from 40-60% at a concentration of 200 microM. For these drugs, a significant correlation was found between the anti-sickling activity and the inhibition of calmodulin-stimulated phosphodiesterase activity. A possibility is raised that deoxy hemoglobin S polymerization is influenced by membrane-linked mechanisms.