Chlorpromazine actions

The multidrug resistance (mdr) reversing effect of the new phenothiazine complexes were tested on mouse T cell lymphoma cell lines. Trifluoperazine (TFP) was much more effective at the same concentration than verapamil. The efficacy of some metal coordination complexes [TFP-Cu(ll) and TFP-V(IV)] exceeded the action of TFP alone. Chlorpromazine (CPZ) or CPZ-Pt(ll) complex had the same or less effect than verapamil or promethazine (Pz) used as a control. 

Many of the neuroleptics are a-adrenoceptor antagonists. Some, like chlorpromazine, block d postsynaptic receptors while clozapine (and risperidone) are as potent at 2 as D2 receptors. There is no evidence that either of these actions could influence striatal or mesolimbic function but NA is considered important for function of the prefrontal cortex and any increase in its release, achieved by blocking a2-mediated autoinhibition, might contribute to a reduction in negative symptoms and provide a further plus for clozapine (see Nutt et al. 1997). Centrally, however, most a2-receptors are found postsynaptically and their function, and the effect of blocking them, is uncertain. 

Certainly clozapine can avoid EPSs by only blocking a fraction of D2 receptors but that seems insufficient on its own to make clozapine so effective in schizophrenia. That is probably achieved by a unique combination of other blocking actions, at Di, D4, 5-HT2, o 2 and possibly other receptors (see Fig. 17.8). It may simply be that clozapine is so effective because it is so dirty , a view held for many years about the first neuroleptic chlorpromazine. Indeed it is unlikely that the varied symptoms of such a complicated disorder could be rectified by manipulating just one NT. 

The administration of low doses of PCP to rodents induces hyperactivity and stereotypy (Chen et al. 1959 ). The observation that neuroleptics such as chlorpromazine, haloperidol, and pimozide, and adrenolytics such as alpha-methyl paratyrosine antagonize these behavioral effects of PCP suggests that they are mediated by facilitation of central dopaminergic neurotransmission (Murray and Horita 1979). The actions of PCP on central dopaminergic neurotransmission may be similar to amphetamine. A dose of PCP (2.5 mg/kg) in rats, which has no effects when given alone, enhances the behavioral effects of 1 and 3 mg/kg of d-amphetamine (Balster and Chait 1978). PCP, like dopamine, has also been shown to suppress plasma prolactin (Bayorh et al. 1983). However, the firm establishment of an excl usive relationship between dopamine neuro-transmission and PCP effects is difficult because of the prominent interactions of this drug with other neurotransmitter systems. 

The answer is d. (Hardman, pp 407-4122) Haloperidol is a butyro phenone derivative with the same mechanism of action as the phe-nothiazines, that is, blockade of dopaminergic receptors. It is more selective for D2 receptors. Haloperidol is more potent on a weight basis than the phenothiazines, but produces a higher incidence of extrapyra-midal reactions than does chlorpromazine. 

Hill, H. F., Bell, E. C., and Wilder, A. (1967) Reduction of conditioned suppression Actions of morphine compared with those of amphetamine, pentobarbital, nalorphine, cocaine, LSD-25, and chlorpromazine. Arch. Int. Pharmacodyn., 165 212-225. 

In addition, other chemicals such as a-adrenergic blocking agents like chlorpromazine (O Flaherty and Thomas 1982 Way and Burrows 1976) or oxygen (Burrows et al. 1973 Sheehy and Way 1968) may be used to enhance the protective action of other antidotes. However, the mechanism of their action is not well understood. Further research for a potent and safe antidote, particularly among smoke inhalation victims who have carbon monoxide poisoning, to mitigate cyanide toxicity is desirable. 

Delay and Deniker observe antipsychotic actions of chlorpromazine. 

In psychiatric practice, chlorpromazine is used in various conditions of psychomotor excitement in patients with schizophrenia, chronic paranoid and also manic-depressive conditions, neurosis, alcohol psychosis and neurosis accompanied by excitement, fear, stress, and insomnia, hi comparison with other neuroleptics, chlorpromazine is unique in that it has an expressed sedative effect. It is sometimes used in anesthesiological practice for potentiating narcosis. It also has moderate anticonvulsant action. The most common synonyms are aminazine, megaphen, largactil, thorazine, prompar, and others. 

As a derivative of phenothiazine, promethazine is structurally and pharmacologically similar to chlorpromazine. It exhibits strong antihistamine activity as well as expressed action on the CNS. It potentiates action of sedative and analgesic drags. 

All antipsychotics block Dj-receptors, but the degree of blockade in relation to actions on other receptors varies greatly. For example, chlorpromazine and... 

Prior to the availability of atypical antipsychotics, typical antipsychotics were used to diminish the acute agitation of mania. Onset of action is typically observed within 3 to 7 days. In a meta-analysis of chlorpromazine trials, efficacy was 54%, which was substantially less than that of lithium, but comparable to that of other mood stabilizers (range, 12%-70%). Risk of extrapyramidal effects and tardive dyskinesia limits the use of these medications beyond the acute phase. 

In pharmacodynamic interactions, the pharmacological effect of a drug is changed by the action of a second drug at a common receptor or bioactive site. For example, low-potency antipsychotics and tertiary amine TCAs have anticholinergic, antihistaminic, a-adrenergic antagonist, and quinidine-Kke effects. Therefore, concurrent administration of chlorpromazine and imipramine results in additive sedation, constipation, postural hypotension, and depression of cardiac conduction. 

Under the effect of chlorpromazine, as 4560 RP was later to be named, patients did not lose consciousness but merely became sleepy and uninterested in everything going on around them and being done to them (Laborit et ti/.. 1952). Laborit and co-workers postulated that this strange central action suggested the use of chlorpromazine in psychiatry, e.g. in sleep therapy, where... 

Antipsychotic drugs with strong sedative clinical effects (e.g. chlorpromazine. clozapine, olanzapine) produce subjective and objective sedation and impair most areas of performance in healthy volunteers, usually at doses far below those typically used in patients. Antipsychotic drugs with little sedative clinical action (e.g. pimozide, sulpiride, amisulpride) produce few subjective and objective effects in healthy... 

In 1954, i.e. about 2 years after the discovery of chlorpromazine in Europe, two American biochemists (Woolley and Shaw) published the hypothesis that schizophrenia and similar psychoses could be based on a disturbance of serotoninergic neurotransmission in the brain. This hypothesis was supported by some facts that had become known shortly beforehand the spectacular psychotropic actions of LSD (lysergic acid diethylamide), which can trigger disturbances in perception, thought and feelings as well as hallucinations in healthy subjects (Stoll, 1947) and the serotonin-antagonistic effects of LSD, i.e. its ability to block the actions of serotonin in various pharmacological tests. 

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