Biochimica et Biophysica Acta (BBA) - General Subjects
Regular paperDifferential effects of neuroleptic agents on hepatic cytochrome P-450 isozymes in the male rat
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Development of a population pharmacokinetic model to predict brain distribution and dopamine D2 receptor occupancy of raclopride in non-anesthetized rat
2018, European Journal of Pharmaceutical SciencesCitation Excerpt :Self-inhibition of metabolism via downregulation of CYP enzymes could be an explanation. In rats, subchronic systemic administration of selective D2 antagonists such as raclopride and other similar benzamides sulpiride and remoxipride could suppress the expression and activity of liver CYP 1A, 1B, 2B, 2C and 3A isozymes (Harkitis et al., 2015; Juřica et al., 2011; Rane et al., 1996), while repeated intracerebral raclopride administration increases CYP 2C activity (Sabová et al., 2013). In addition to modifying systemic PK, chronic administration of raclopride (via subcutaneous osmotic pump) also increases [3H]-raclopride binding sites in rat striatum (See et al., 1990).
The role of brain noradrenergic system in the regulation of liver cytochrome P450 expression
2013, Biochemical PharmacologyCitation Excerpt :Hence it seems conceivable that psychotropic drugs can affect liver cytochrome P450 via neuroendocrine regulation which, in turn, may lead to metabolic drug-drug interactions. It has been shown that tricyclic antidepressants increase antipyrine clearance and accelerate the metabolism of benzphetamine and ketotifen [72,73], while phenothiazine neuroleptics inhibit steroid metabolism and produce some adverse endocrine effects [74,75]. Therefore patients receiving drugs acting on catecholaminergic systems should be carefully monitored for any possible drug interactions (concerning efficacy and safety) during polytherapy with cytochrome P450 substrates.
Effect of classic and atypical neuroleptics on cytochrome P450 3A (CYP3A) in rat liver
2012, Pharmacological ReportsCitation Excerpt :Some literature data indicate that neuroleptics affect CYP3A activity. Two-week treatment with clozapine in a dose substantially exceeding the pharmacological/therapeutic one (114 mg/kg/day) increased the level and activity of CYP3A1 in rats, whereas sulpiride (137 mg/kg/day) and remoxipride (31 mg/kg/ day) produced a decrease in the level of this enzyme [24]. Another study conducted by Tateishi et al. [28], who administered chlorpromazine and thioridazine in a relatively high dose of 20 mg/kg intraperitoneally (ip) for 4 days, showed that chlorpromazine did not change the total level of CYP, but induced CYP3A, whereas thioridazine reduced the total level of CYP, as well as the level and activity of CYP3A.
Effect of neuroleptics on cytochrome P450 2C11 (CYP2C11) in rat liver
2011, Pharmacological ReportsCitation Excerpt :The above-mentioned hormone plays a crucial role in the positive regulation of male rat CYP2C11 [1, 22, 30, 40]. The results obtained in the present study are also in line with other observations indicating down-regulation of CYP2C11 in rats after 2-week treatment with the selective antagonists of dopaminergic D2 receptors, sulpiride and remoxipride and after a 4-day treatment with the less specific dopaminergic D2 receptor-blocking neuroleptic thioridazine [33, 41]. However, the other phenothiazines tested, i.e., promazine and chlorpromazine, do not produce any significant effect on CYP2C11 activity when administered in vivo for two weeks.
Autism spectrum disorders may be due to cerebral toxoplasmosis associated with chronic neuroinflammation causing persistent hypercytokinemia that resulted in an increased lipid peroxidation, oxidative stress, and depressed metabolism of endogenous and exogenous substances
2010, Research in Autism Spectrum DisordersRegulation of liver cytochrome P450 by activation of brain dopaminergic system: Physiological and pharmacological implications
2008, Biochemical PharmacologyCitation Excerpt :The obtained results indicate that drugs affecting brain dopaminergic D2 receptors may change CYP activity in the liver. Accordingly, neuroleptics which are selective (sulpiride, remoxipride) or non-selective (phenothiazines) D2 receptor antagonists down-regulated liver CYP2C11 and CYP3A expressions after systemic administration to rats [52,53]. Hence, via stimulation (e.g. bromocriptine) or inhibition (e.g. neuroleptics) of the neuroendocrine pathways dopaminergic agents may regulate liver CYP, thus affecting the metabolism of endogenous substances (e.g. steroids) and clinically important drugs (e.g. psychotropics), which in turn modifies the final pharmacological effect.