Synergy between a non-neuroleptic thioxanthene stereo-isomer and penicillin in vivo

Some neuroleptic drugs of the phenothiazine and thioxanthene groups have an antimicrobial effect in vitro. This is also true for neuroleptically inactive stereo-isomeric analogs of the thioxanthenes e.g. trans(E)-clopenthixol (t-CPT). In a murine pneumococcus peritonitis model t-CPT demonstrated a slight, but non-significant antibacterial effect in doses of 0.3-0.9 mg per mouse, while higher doses seemed to enhance the bacterial virulence. If combined with subtherapeutic doses of penicillin, a significantly higher survival rate was obtained compared with either drug given alone. In vitro studies demonstrated a similar synergistic effect. These results indicate that at least one non-neuroleptic thioxanthene stereo-isomer has an antibiotic potential also in vivo. The mechanism of action is not known.