Direct effects of neuroleptics on the activity of CYP2A in the liver of rats.
Journal Title: Pharmacological Reports - Year 2005, Vol 57, Issue 6
Abstract
The aim of the present study was to investigate the influence of classic and atypical neuroleptics on the activity of rat CYP2A measured as a rate of testosterone 7alpha-hydroxylation. The reaction was studied in control liver microsomes in the presence of neuroleptics, as well as in microsomes of rats treated intraperitoneally (ip) for one day or two weeks (twice a day) with pharmacological doses (mg/kg) of the drugs (promazine, levomepromazine, thioridazine, perazine 10, chlorpromazine, haloperidol 0.3, risperidone 0.1, sertindole 0.05), in the absence of the neuroleptics in vitro. Most of the neuroleptics added in vitro to control liver microsomes decreased the activity of the rat CYP2A. Chlorpromazine (K(i) = 11 muM) was the most potent inhibitor of the rat CYP2A among the studied drugs, whose effect was more pronounced than that of the other tested phenothiazines (K(i) = 41-83 muM), haloperidol (K(i) = 190 muM) or sertindole (K(i) = 78 muM). Risperidone was not active in this respect. The investigated neuroleptics when given to rats in vivo for one day or two weeks - did not produce any indirect inhibitory effect on CYP2A via other mechanisms. The obtained results show direct inhibitory effects of phenothiazine neuroleptics on the activity of CYP2A in rat liver, which may be of physiological importance for the metabolism of testosterone, considering simultaneous inhibition of CYP2C11 and CYP3A by those drugs.
Authors and Affiliations
Anna Haduch, Jacek Wójcikowski, Władysława Daniel
Keywords
Related Articles
- EP ID EP118278
- DOI -
- Views 100
- Downloads 0
Anti-inflammatory effects of LASSBio-998, a new drug candidate designed to be a p38 MAPK inhibitor, in an experimental model of acute lung inflammation.
We investigated the effects of LASSBio-998 (L-998), a compound designed to be a p38 MAPK (mitogen-activated protein kinase) inhibitor, on lipopolysaccharide (LPS)-induced acute lung inflammation in vivo. BALB/c mice were...
Antithrombotic effect of captopril and enalapril in old rats.
In the present study, we have shown considerably accelerated thrombosis in old rats in comparison with adult rats, which may be related to the impaired hemostatic balance in these animals. In old rats, captopril and enal...
Effects of bupropion on the reinstatement of nicotine-induced conditioned place preference by drug priming in rats.
Nicotine is one of the most widely consumed psychoactive drugs, and its consumption is currently associated with other drugs of abuse, such as opioids. The aim of the present study was to evaluate the efficacy of the aty...
Involvement of 5-hydroxytryptamine type 3 receptors in sevoflurane-induced hypnotic and analgesic effects in mice.
In the present study, we investigated the role of 5-hydroxytryptamine type 3 (5-HT(3)) receptors in hypnosis and analgesia induced by emulsified sevoflurane. A mouse model of hypnosis and analgesia was established by an...
Kynurenic acid protects against the homocysteine-induced impairment of endothelial cells.
Kynurenic acid (KYNA) is a tryptophan metabolite produced in the kynurenine pathway. In the central nervous system, KYNA exerts neuroprotective and anticonvulsant effects by mechanisms associated with its antagonist acti...