title: Phenothiazine molecule provides the basic chemical structure for various classes of pharmacotherapeutic agents.
abstract: The chemical structure of phenothiazine provides a most valuable molecular template for the development of agents able to interact with a wide variety of biological processes. Synthetic phenothiazines (with aliphatic, methylpiperazine, piperazine-ethanol, piperazine-ethyl, or piperidine side-chain) and/or phenothiazine-derived agents e.g., thioxanthenes, benzepines, imonostilbenes, tricyclic antidepressants, dimetothiazine, and cyproheptadine have been effective in the treatment of a number of medical conditions with widely different etiology. These include various currently clinically used drugs for their significant antihistamic, antipsychotic, anticholinergic (antiparkinson), antipruritic, and/or antiemetic properties. They are also employed, although to a minor extent, as antidepressants, antispasmodics, analgesics, and antiarrhythemics. Some of these agents are also useful as anti-inflammatory, coronary vasodilator, radioprotective, sedative, antitussive, and skeletal muscle-relaxing medication. Still, others show different degrees of effectiveness as antibacterials, anthelmintics, antimalarials, or local anesthetics; a few are valuable in the control of acute migraine attacks and intractable hiccough. Adding to the seemingly ever-expanding therapeutic use of phenothiazine derivatives, a number of "old" and newly synthesized compounds e.g., "half-mustard-type" and benzo[alpha]phenothiazines, appear to be helpful as multidrug resistance modifiers, a property of particular importance in cancer chemotherapy. Some phenothiazines inhibit human plasmatic leucine-enkephalin aminopeptidase(s), enzymes known to regulate the turnover rate of a wide range of bioactive substances. These findings could lead to the design of new therapeutic treatment modalities for conditions such as Alzeimer's and Creutzfeldt-Jakob disease. Hopefully, this work will help to the rational design of new and improved pharmacological approaches based on a better understanding of the correlation between chemical structure, pharmacodynamic properties, and pharmacological activity of various phenothiazines and phenothiazine-derived classes of drugs.
authors.affiliation: Department of Cellular and Molecular Pharmacology, Rosalind Franklin University of Medicine and Science/The Chicago Medical School, N. Chicago, IL 60064, USA.
authors.forename: Aron D
authors.initials: AD
authors.lastname: Mosnaim
authors.forename: Vasant V
authors.initials: VV
authors.lastname: Ranade
authors.forename: Marion E
authors.initials: ME
authors.lastname: Wolf
authors.forename: Javier
authors.initials: J
authors.lastname: Puente
authors.forename: M
authors.initials: M
authors.lastname: Antonieta Valenzuela
mesh_terms: D000818:Animals; D014150:Antipsychotic Agents / Q000737:chemistry / Q000627:therapeutic use*; D006801:Humans; D010640:Phenothiazines / Q000737:chemistry / Q000627:therapeutic use*; D013329:Structure-Activity Relationship
chemical_list: D014150:Antipsychotic Agents; D010640:Phenothiazines