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PubMedDate not supplied

Effects of butaclamol, clopenthixol, mepromazine and cannabinol stereoisomers on apoptosis induction.

The efflux pump of multidrug resistant mdr cells have different sensitivities to some stereoisomeric forms of CNS-active compounds. The ABC transporters of mdr cells were more sensitive to (-)butaclamol than to its stereoisomeric counterpart (8), which may function to alter the membrane structure. We suppose that the drug-accessible membrane structure possesses an important role in the induction (or prevention) of apoptosis. Therefore the apoptosis-inducing effect of three stereoisomeric pairs was studied on mouse lymphoma cells. In these experiments levo- and dextromepromazine had similiar effects. The cis- and trans-clopenthixol were less effective in apoptosis induction than the 12H-benzo(a)-phenothiazine used as a positive control. The effect of stereoisomeric pairs on induced apoptosis was studied when the cells were exposed to the stereoisomers for 60 minutes before subjection apoptosis induction by benzo(a)phenothiazine, a well-known apoptosis inducer. Then the pretreated cells were exposed to 12H-benzo(a)-phenothiazine for 60 minutes. The samples were washed and incubated for 24 hours. The cells were stained with annexin-V-FITC and propidium iodine and investigated by flow cytometry. The mdr cells with increased membrane integrity may result in the preferential killing of multidrug resistant cancer cells in the presence of some stereoisomers.

Animals↗
PubMedDate not supplied

[Comparative study of the effect of some psychotropic substancces on the activity of brain Na+, K+-ATPase in vitro].

The activity of Na+, K+-ATPase from bovine brain in vitro was studied as affected by some neuroleptics (levomepromazine, chlorpromazine, perphenazine and haloperidol), antidepressants (imipramine and iproniazid) and psychostimulants (amphetamine) as well as by benactyzine and procaine. The degree of the enzyme inhibition by these drugs estimated by means of I 50 and apparent inhibitor constants (Ki) or rate constants (k) was different. Sensitivity of the brain Na+, K+-ATPase to the drugs decreased in the following order: levomepromazine, chlorpromazine, perphenazine, haloperidol, imipramine, iproniazid, benactyzine, procaine and amphetamine. Competition for the enzyme was revealed between sodium and some of the drugs investigated (levomepromazine, chlorpromazine, perphenazine and impramine) as well as between potassium and other drugs (haloperidol, genactyzine and amphetamine). It is suggested that the inhibition of the brain Na+, K+-ATPase by psychotropic drugs may be a part in the biochemical mechanism of their sedative-tranquilizing activity.

Adenosine Triphosphatases↗
PubMed1976

[Hemodynamic study of postural regulation in the dog treated or not treated with levomepromazine].

Analysis of hemodynamic parameters in untreated and treated dogs (levomepromazine 5 mg/kg i.v.) during supine and erect position showed, 1) that the regulation of cerebral blood flow remained in the anaesthetized (pentobarbital 25 mg/kg i.v.) dogs ; 2) that the sympathetic reaction induced different effects in various vascular regions ; 3) that levomepromazine induced an impairement of the mechanisms involved in the regulation of the encephalic irrigation.

Animals↗