Chlorpromazine interaction

Giouinard G, Pinard G, Prenoveau Y, Tetreault L. Alpha methyldopa-chlorpromazine interaction in schizophrenic patients. Curr Ther Res ( 97i) 15,60-72. 

A and solid state NMR study was undertaken to study chlorpromazine interaction with phosphatidylserines. Chlorpromazine is widely used as an antipsychotic drug. and solid state NMR techniques were employed to study phospholipid bilayers with and without chlorpromazine. 

Chlorpromazine arrests cultured cells in mitosis and disorganises the organised microtubule structure produced by cyclic adenosine monophosphate (Poffenbarger and Fuller 1977). It causes a reduction in the number of microtubules in spinal ganglion cells (Edstrom et al. 1973, Thyberg et al. 1977) and neuroblastoma cells (EdstrOm et al. 1975) in vitro. The micellar form of chlorpromazine interacts preferentially with one site on brain tubulin (Gann et al. 1981). Ghlorpromazine has been shown to bind reversibly to tubulin prepared from mouse brain via two well-resolved processes (Hin-... 

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. 

Toxicity is remarkably low for a compound of such activity. In mice, the LDso value is about three times that of chlorpromazine [166] while none of the effects of the latter drug on the myocardium, liver, skin or eye have appeared in the studies of oxypertine. It is, however, still too early to appraise its chronic toxicity in man. As indicated earlier, dangerous interactions are likely to follow concurrent use of a MAO inhibitor, though simultaneous use of anti-Parkinsonism drugs, for example, to control the relatively minor extra-pyramidal symptoms seems to present no unusual problems. Hypotension may occasionally occur with high doses. 

Compounds 40—43 interacted with bovine brain-calmodulin as detected in a SDS-PAGE electrophoresis. Calmodulin treated with the lactones had lower electrophoretic mobility than untreated calmodulin. The effect was comparable to that of chlorpromazine, a well known calmodulin inhibitor. In addition, different concentrations of compounds 40 and 41 inhibited calmodulin-depen dent PDEl. The inhibitory activity of herbaru-mins 1 (IC50 = 14.2 xM) and II (IC50 = 6.6 xM) was higher than that of chlorpromazine (IC50 = 9.8... 

W Caetano, M Tabak. Interaction of chlorpromazine and trifluoperazine with anionic sodium dodecyl sulfate (SDS) micelles electronic absorption and fluorescence studies. J Coll Inter Sci 225 69—81, 2000. 

Clinicians should be aware of a few drug interactions with Zolpidem. Flumazenil acts as an antagonist to the hypnotic effects of zolpidem. There is decreased alertness when zolpidem is combined with cimetidine. There is an increase in anterograde amnesia in volunteers treated with a combination of imipramine and zolpidem. Haloperidol, ranitidine, chlorpromazine, warfarin, and digoxin, along with cimetidine and flumazenil, do not alter the pharmacokinetics of zolpidem (Salva and Costa, 1995). 

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. 

The clinical effect of a tyramine interaction Ccheese reactionO is a hypertensive crisis flushing severe throbbing headache severe hypertension tachycardia pallor. There is a risk of cerebral haemorrhage. Treatment is by a 1-adrenoceptor antagonist (phentolamine or chlorpromazine) which is usually given intravenously. 

Several other examples of drug-membrane interactions have been reported. Using X-ray diffraction techniques, interactions with tetracyclines [75], pindolol [76], and chlorpromazine [77, 78] have been described. In these studies, it was shown that in the presence of chlorpromazine the bilayer thickness or lipid head group separation in DPPC liposomes is only 30 A, which is about 20 A smaller than two fully extended DPPC molecules. Chlorpromazine produced an interdigitated phase, which is in agreement with the observed effect of chlorpromazine on the shape of erythrocytes. 

Tab. 5.27 Correlation coefficients between drug-membrane interaction parameters and biological data of the seven modifiers studied, (c/s- and trans-flupentixol, chlorpromazine, trifluoperazine, triflupromazine, imipramine, and quinacrine). Chlorpromazine was omitted from regression corresponding to the MCF-7/DOX cell line. Quinacrine data were not available for the P388/DOX cell line. (Reprinted from Tab. 2 of ref. 11 7, with permission from Bertelsmann-Springer)...

Selective serotonin reuptake inhibitors (SSRIs), such as fluoxetine, interact with drugs including clarithromycin, warfarin, phenelzine, benzotropine, chlorpromazine, diazepam, and cyproheptadine. Cigarette smokers metabolize SSRIs faster. 

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