title: Synergy between a non-neuroleptic thioxanthene stereo-isomer and penicillin in vivo.
abstract: 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.
authors.affiliation: Department of Clinical Microbiology, Herley Hospital, Denmark.
authors.forename: J E
authors.initials: JE
authors.lastname: Kristiansen
authors.forename: O
authors.initials: O
authors.lastname: Sebbesen
authors.forename: N
authors.initials: N
authors.lastname: Frimodt-Møller
authors.forename: T
authors.initials: T
authors.lastname: Aaes-Jørgensen
authors.forename: E F
authors.initials: EF
authors.lastname: Hvidberg
mesh_terms: D000818:Animals; D003006:Clopenthixol / Q000008:administration & dosage* / Q000493:pharmacokinetics; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D051379:Mice; D008826:Microbial Sensitivity Tests; D010406:Penicillins / Q000008:administration & dosage*; D011008:Pneumococcal Infections / Q000188:drug therapy*; D013237:Stereoisomerism; D013296:Streptococcus pneumoniae / Q000187:drug effects; D013892:Thioxanthenes / Q000008:administration & dosage*
chemical_list: D010406:Penicillins; D013892:Thioxanthenes; D003006:Clopenthixol