Chlorpromazine chemical structure

The conventional (or classical) neuroleptics comprise two classes of compounds with distinctive chemical structures 1. the phenothiazines derived from the antihistamine promethazine (prototype chlorpromazine), including Ltillmann, Color Atlas of Pharmacology 2000 Thieme All rights reserved. Usage subject to terms and conditions of license. 

Unlike reserpine, chlorpromazine has neither a serotonin-like chemical structure nor does it release serotonin from nerve raidings. 

The tricyclic antidepressants (Table 6—5) were so named because their organic chemical structure contains three rings (Fig. 6—25). The tricyclic antidepressants were synthesized about the same time as other three-ringed molecules that were shown to be effective tranquilizers for schizophrenia (i.e., the early antipsychotic neuroleptic drugs such as chlorpromazine) (Fig. 6—26). The tricyclic antidepressants were a disappointment when tested as antipsychotics. Even though they have a three-ringed structure, they were not effective in the treatment of schizophrenia and were almost... 

Figure 10.1 Chemical structure of chlorpromazine and imipramine (taken from Healy 1997, p. 51)...

The introduction of the phenothiazine derivative, chlorpromazine, has started a dramatic improvement in the clinical treatment of schizophrenia. During the past four decades, beside phenothiazines, various antipsychotics having different chemical structures have been identified and introduced into clinical practice (e.g., butyrophenones and benzamides). These drugs ( typical antipsychotics ) decreased the duration of hospitalizations and, with maintenance treatment, reduced the risk of relapse and re-hospitalization. However, they had significant adverse side effects such as tardive dyskinesia, orthostatic hypotension, prolactin increase, and QT prolongation. 

Fig. 13.1 Chemical structure of clozapine, some of its structural analogues, typical (chlorpromazine, haloperidol) and atypical antipsychotics (risperidone, ziprasidone, sertindole and amisulpride) unrelated to clozapine.

Molnar et al. [69] studied antibacterial effect and plasmid curing property of several phenothaizines and tried to correlate these functions with respect to their chemical structure. They observed that diethazine, amitriptyline, and impipramine showed bacteriostatic and bactericidal effect on different bacteria. Chlorpromazine sulfoxide and fluorescein were ineffective even at 1000 Ag/ml. The antibacterial compounds deleted at 40-70% frequency the F lac-t- plasmid of Escherichia coli K12 Le-140. Similar plasmid elimination potentiality by phenothiazines was reported by the same group of authors in 1982 [72],... 

Chart 1.9 Chemical structures of chlorpromazine (20), reserpine (21), haloperidol (22). 

SAR of Ethopromazine. Another wonderful and dramatic appropriate example of appreciable pharmacologic differences existing between compound which are practically-look-alikes is the usage ofphenothiazine structural analogue ethopropazine to control and treat the extrapyramidal Parkinson like syndrome caused by antipsychotics, for instance chlorpromazine — the well-known neuroleptic chlorpromazine (Chapter 18). A close examination of the prevailing chemical structures of the two types... 

Figure 5.6 Chemical structure (a) and graph representation (b) of the antipsychotic drug chlorpromazine.

Most of the older antidepressants are called tricyclic because their chemical nucleus has the basic tricyclic structure of the original pheno-thiazine neuroleptic, chlorpromazine, or Thorazine (Bassuk et ah, 1977 Pauker, 1981). Of extreme importance, the antidepressant amoxapine (Asendin) is turned into a neuroleptic in the body, producing the same problems as any other neuroleptic, including tardive dyskinesia (chapters 3 and 4). 

Figure 1 Physical and chemical stimuli affecting the gating of bacterial MS channels. (A) The structure of the pentameric MscL channel (left) and a channel monomer (right) from Mycobacterium tuberculosis according to the 3-D structural model of a closed channel (7). MscL is activated by membrane stretch, amphipaths (e.g., lysophopholipids, chlorpromazine, and trinitrophenol) and parabens. The channel activity is inhibited by Gd + and static magnetic fields (SMF) and is modulated by temperature and intracellular pH (3). (B) The structure of the MscS heptamer (left) and the channel monomer (right) from E. coli based on the 3-D structural model of MscS (8) most likely depicting an inactive or desensitized functional state of the channel (3). MscS is activated by membrane stretch, amphipaths, and parabens and is modulated by voltage. The activity of the channel is inhibited by Gd + and high hydrostatic pressure (HHP) (3). The arrows point at membrane structures (i.e., channel protein and/or lipid bilayer) affected by the specific stimuli.

Association is a feature of chlorpromazine base and related derivatives in the supercooled state.< Such associations may be preceded by the formation of intramolecular complexation, i.e., different regions of the same molecular species acting as donor and acceptor. It is interesting to note that in this context the solid state structure of chlorpromazine base is not symmetrical, presumably due to van der Waals or perhaps weak charge transfer interaction between the chlorine ring substituent and the side-chain amine group. Donor and acceptor properties can be modified by chemical substitution, and are sensitive to steric hindrance. In a way, intramolecular charge transfer reproduces the effect of delocalized electrons. ... 

The phenothiazine sulfides were obtained from West Chemical Company. Their preparation has been described by Nodiff and Cantor, Their structures, and that of chlorpromazine hydrochloride (CPZ.HCl), are shown in Fig. 2. 

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