Chlorpromazine phenothiazine neuroleptic

Although the discovery that chlorpromazine and related phenothiazine neuroleptics were effective in the treatment of schizophrenia was... 

Laborit in the early 1950s is credited with the observation that chlorpromazine had a "calming effect in disturbed schizophrenic patients and since that time psychopharmacologists have sought to explain the mechanism of action of neuroleptic drugs. Carlsson and Linquist in 1963 demonstrated a link between the therapeutic effects of the phenothiazine neuroleptics and an inhibition of dopamine receptor function. This led to... 

In the phenothiazine series of neuroleptics, thioridazine has less antimuscarinic potency than chlorpromazine, but appears to be equally active as an antagonist of 5-HT2 and D2 receptors like chlorpromazine, however, it is a potent alpha] adrenoceptor antagonist. In contrast, the potent phenothiazine neuroleptic perphenazine is only slightly less selective in blocking D2 receptors than haloperidol but, unlike the latter, has a greater antagonistic effect on histamine receptors. 

Phenothiazine neuroleptics (e.g. chlorpromazine, thioridazine) + vasodilators and antihypertensive drugs —> increased hypotensive effects due to increased peripheral vasodilation. 

Rare, familial hyperthermia (41 °C) associated with inhalation anaesthetics, muscle relaxants, tricyclic antidepressants, phenothiazine neuroleptics (particularly chlorpromazine) monoamine oxidase inhibitors and haloperidol. 

Chlorpromazine] (phenothiazine) Synthetic CaM (D-K) [antiemetic, antipsychotic, neuroleptic, tranquillizer]... 

Daniel et al. [136] investigated the effects of phenothiazine neuroleptics on the rate of caffeine demethylation and hydroxylation in the rat liver. The influence of several phenothiazine neuroleptics, such as chlorpromazine, levomepromazine, thioridazine and perazine, on the cytochrome P-450 activity was measured by means of the caffeine oxidation in rat liver micro-somes. The obtained results demonstrated that all of the neuroleptics under study competitively inhibited their caffeine oxidation in the rat liver, although their potency to inhibit the particular metabolic pathways was not equal. Levomepromazine exerted the most potent inhibitory effect on the caffeine oxidation pathways, and had the most pronounced influence on 8-hydroxylation. 

Chlorpromazine is well absorbed mainly from the jejunum. It is extensively metabolized in the liver, which produces several active metabolites. When given intramuscularly, the phenothiazine neuroleptics avoid metabolic degradation (first-pass metabolism), making them more beneficial as long-acting depot antipsychotics (see Table 2). 

Desager JP, Hulhoven R, Harver C, Hermann P, Guillet P, ThierceUn JF. Possible interactions between zolpidem, a new sleep inducer and chlorpromazine, a phenothiazine neuroleptic. Psychopharmacology (Berl) (1988) 96,63-6. 

The role of fluonne in the development of CNS agents has been reviewed [14] Ruonnated phenothiazines, typified by fluphenazine (7[Pg.1121]

Chlorpromazine is technically described as a phenothiazine, as are thioridazine and fluphenazine. Together with their structural analogues the thioxanthenes (e.g., clopenthixol) and the butyrophenones (e.g., haloperidol), the phenothiazines comprise the three major families of typical neuroleptics. They were developed in the late 1950s and early 1960s (Table 11.3). All these drugs block dopamine receptors, principally the D2 subtypes, with an affinity that correlates highly (r = +0.90) with their clinical... 

Phenothiazines A family of neuroleptics which includes chlorpromazine and fluphenazine. 

Whatever the underlying causes may be, neuroleptic medications are the most effective treatment for schizophrenia. All antipsychotic medications have some form of dopamine receptor antagonism and they are distinguished by their chemical class. The phenothiazines include chlorpromazine (Thorazine), thioridazine (Mellaril), mesoridazine (Serentil), trifluoperazine (Stelazine), fluphenazine (Prolixin), and prochlorperazine (Compazine). The thioxanthenes include chlorprohixine (Taractan) and thiothixene (Navane). Butyrophenones are represented by haloperidol (Haldol). Loxapine (Loxitane) is a dibenzoxapine, and molindone (Moban) is a dihydroindolone. 

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. 

Phenothiazine derivatives have found many applications in todays chemical industry they have been and are used primarily as dyestuffs, antioxidants and in pharmaceutical preparations. This application is due to the discovery of their neuroleptic activity (1 ) (e.g. Chlorpromazine), but allergic skin reactions and ocular opacity are known to occur during therapy. 

In recent years traditional neuroleptics, as exemplified by chlorpromazine, have been structurally modified to produce drugs with greater affinity for dopamine receptors while retaining some of their activity on other receptor systems (e.g. on alpha] adrenoceptors, 5-HT2 receptors and histamine] receptors). In the non-phenothiazine series, a high degree of specificity for the D2 receptors has been achieved with sulpiride and pimozide, with haloperidol showing antagonistic effects on the 5-HT2 and alpha] adrenoceptors in addition to its selectivity for D2 receptors. The czs-(Z) isomers of the thioxanthines are potent neuroleptics that, in addition to... 

A variety of drugs that block DA receptors are available for clinical use, and even more for experimental purposes. These drugs, also referred to as neuroleptics, include phenothiazines (e.g., chlorpromazine), thioxanthenes (e.g., chlorprothixene), butyrophenones (e.g., haloperidol), diphenylbutylpiperidines (e.g., pimozide), and dibenzodiazepines (e.g., clozapine). The major medical applications for these drugs are in the treatment of severe psychiatric illnesses, certain movement disorders, emesis and intractable hiccough. 

Kristiansen and Blom [56] examined various types of phenothiazines for antibacterial effect on 61 Gram-positive and Gram- negative bacterial strains in vitro the investigated phenothiazines were two neuroleptic drugs, fluphenazine and chlorpromazine, and an antihistaminic drug, prometha-... 

Qll Other neuroleptic agents include phenothiazines, such as chlorpromazine, promazin and thioridazine, and thioxanthines, such as flupenthixol. The non-specific blockade of dopaminergic receptors afforded by these drugs leads to development of side effects, such as endocrine dysfunction and extrapyramidal motor symptoms. The unwanted antagonism of motor tracts results in extrapyramidal side effects, such as Parkinsonism and tardive dyskinesia. The latter is associated with involuntary movements of the face, limbs and trunk. Chronic neuroleptic therapy can inhibit the release of GABA. This in turn leads to changes in mobility. 

Antipsychotics are also referred to as neuroleptic drugs, such as haloperi-dol, phenothiazines (e.g. chlorpromazine, promazin and thioridazine) and thioxanthines (e.g. flupenthixol). All theses agents are used in treating the symptoms and are mostly successful with positive symptoms. 

The effects of neuroleptic drugs on fertility are not clear many of the data are controversial, often being based on animal studies, for example reduction in male rat copulation by chlorpromazine. However, oligospermia, polyspermia, necrospermia, and reduced sperm motility have been reported with various phenothiazines and butyro-phenones these are likely to improve after withdrawal (473). Furthermore, fertility may be impaired by neuroleptic drugs, since they increase prolactin concentrations and can cause amenorrhea (4). 

Neuroleptics with basic side-chains (chlorpromazine hydrochloride [2102], profenamine hydrochloride [2107]) shift slightly towards shorter wavebands than the parent substance (phenothiazine [203]). 

---