Phenobarbital receptor

Kodama S, Negishi M (2006) Phenobarbital confers its diverse effects by activating the orphan nuclear receptor CAR. Drug Metab Rev 38 75-87... 

Consider propofol pharmacotherapy, as it agonizes GABA-A receptors and antagonizes NMDA receptors. Phenobarbital can be used as an alternative... 

Age-related variations in central nervous system (CNS) neurotransmitter production and receptor sensitivity are the most likely explanations for the pharmacodynamic differences observed between children and adults following administration of psychotropic medications [39a], Children have lower phenobarbital ratios than adults, and the ratio increases with gestational age [40,41]. Conversely, a lower therapeutic range for children has been identified for cyclosporine, phenytoin, and digoxin [42]. 

Date M et al. Differential expression of transforming growth factor-/ and its receptors in hepatocytes and nonparenchy-mal cells of rat liver after CC14 administration. J Hepatol 1998 28 572-581. Frueh FW et al. Extent and character of Phenobarbital-mediated changes in gene expression in the liver. Mol Pharmacol 1997 51 363-369. 

Phenobarbital may act by interacting with GABA receptors, blocking high voltage-activated Ca channels, and blocking a-amino-3-hydroxy-5-meth-ylisoxazole-4-propionic acid and kainate receptors. 

Sugatani J, Kojima H, Ueda A et al (2001) The phenobarbital response enhancer module in the human bilirubin UDP-glucuronosyltransferase UGT1A1 gene and regulation by the nuclear receptor CAR. Hepatology 33 1232-1238... 

X receptor heterodimer activates the phenobarbital-responsive enhancer module of the CYP2B gene. Molecular and Cellular Biology, 18,... 

Buspirone (BuSpar) [Anxiolytic] WARNING Closely monitor for worsening depression or emergence of suicidality Uses Short-term relief of anxiety Action Antianxiety antagonizes CNS serotonin receptors Dose Initial 7.5 mg PO bid T by 5 mg q2-3d to effect usual 20-30 mg/d max 60 mg/d Contra w/ MAOI Caution [B, /-] Avoid w/ severe hepatic/renal insuff Disp Tabs SE Drowsiness, dizziness, HA, N, EPS, serotonin synd, hostility, depression Notes No abuse potential or physical/psychologic d endence Interactions T Effects W/ erythromycin, clarithromycin, itraconazole, ketoconazole, diltiazem, verapamil, grapefruit juice effects W/ carbamazepine, rifampin, phenytoin, dexamethasone, phenobarbital, fluoxetine EMS T Sedation w/ concurrent EtOH use grapefruit juice may T risk of adverse effects OD May cause dizziness, miosis, N/V symptomatic and supportive... 

The anticonvulsant activity of diazepam, assessed by its protection against pentylenetetrazole-induced tonic convulsions, was strongly reduced in ai-(HIOIR) mice compared to wild-type animals (Rudolph et al. 1999). Sodium phenobarbital remained fully effective as anticonvulsant in ai(HlOlR) mice. Thus, the anticonvulsant activity of benzodiazepines is partially but not fuUy mediated by ai receptors. The anticonvulsant action of zolpidem is exclusively mediated by ai receptors, since its anticonvulsant action is completely absent in ai(HlOlR) mice (Crestani et al. 2000). 

Different sites on the same receptor (e.g., diazepam and phenobarbital both bind to the GABA-A receptor, but at different sites benzodiazepine site versus barbiturate site). 

Figure 4.12 The GABA-A channel functions as a receptor for many multiple different drug classes, including benzodiazepines (e.g., diazepam) and barbiturates (e.g., phenobarbital). There is also a steroid-binding site on the GABA-A channel which may be useful in the future design of general anesthetics.

Ward, J.M., Peters, J.M., Perella, C.M. Gonzalez, F.J. (1998) Receptor and nonreceptor-mediated organ-specific toxicity of di(2-ethylhexyl)phthalate (DEHP) in peroxisome proliferator-activated receptor a-null mice. Toxicol. Pathol., 26, 240-246 Weghorst, C.M., Devor, D.E., Henneman, J.R. Ward, J.M. (1993/94) Promotion of hepatocellular foci and adenomas by di(2-ethylhexyl) phthalate and phenobarbital in C3H/HeNCr mice following exposure to N-nitrosodiethylamine at 15 days of age. Exp. Toxicol. Pathol, 45, 423-431... 

Chen Y, Ferguson SS, Negishi M, Goldstein JA. Induction of human CYP2C9 by rifampicin, h5 perforin, and phenobarbital is mediated by the pregnane X receptor. J Pharmacol Exp Ther 2004 308(2) 495-501. 

Sueyoshi T, Negishi M Phenobarbital response elements of cytochrome P450 genes and nuclear receptors. Annu Rev Pharmacol Toxicol 2001 41 123. [PMID 11264453]... 

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