Abstract:
:Endogenous cannabinoid ligands and cannabinoid CB1 receptor agonists have been shown to exert anticonvulsant effects in various experimental models of epilepsy. The purpose of this study was to determine the effects of arachidonyl-2'-chloroethylamide (ACEA-a highly selective cannabinoid CB1 receptor agonist) on the protective action of clonazepam, ethosuximide, phenobarbital, and valproate against pentylenetetrazole (PTZ)-induced clonic seizures in mice. To ascertain any pharmacokinetic contribution of ACEA to the observed interactions between tested drugs, free (non-protein bound) plasma and total brain concentrations of the antiepileptic drugs were estimated. Additionally, acute adverse-effect profiles of the combination of ACEA and different classical antiepileptic drugs (clonazepam, ethosuximide, phenobarbital and valproate) with respect to motor performance, long-term memory and skeletal muscular strength were measured. Results indicated that ACEA (10mg/kg, i.p.) co-administered with phenylmethylsulfonyl fluoride (PMSF-a substance protecting ACEA against degradation by the fatty-acid hydrolase; 30mg/kg, i.p.) significantly potentiated the anticonvulsant activity of ethosuximide, phenobarbital and valproate in the mouse PTZ-induced clonic seizure model by reducing their median effective doses (ED(50) values) from 122.8mg/kg to 71.7mg/kg (P<0.01; for ethosuximide), from 13.77mg/kg to 5.26mg/kg (P<0.05; for phenobarbital), and from 142.7mg/kg to 87.3mg/kg (P<0.05; for valproate), respectively. In contrast, ACEA (10mg/kg, i.p.) in combination with PMSF (30mg/kg, i.p.) had no impact on the protective action of clonazepam against PTZ-induced seizures in mice. However, ACEA (10mg/kg)+PMSF (30mg/kg) considerably increased free plasma and total brain concentrations of ethosuximide and valproate in mice suggesting a pharmacokinetic nature of interaction between drugs. In contrast, free plasma and total brain concentrations of clonazepam and phenobarbital remained unchanged after ACEA+PMSF administration and thus, indicating pharmacodynamic interactions. Moreover, none of the examined combinations of ACEA (10mg/kg, i.p.)+PMSF (30mg/kg, i.p.) with clonazepam, ethosuximide, phenobarbital, and valproate (at their ED(50) values from the PTZ-induced seizure test) affected motor coordination in the chimney test, long-term memory in the passive avoidance task, and muscular strength in the grip-strength test in mice, indicating no possible acute adverse effects in animals. In conclusion, pharmacodynamic enhancement of the anticonvulsant potency of phenobarbital by ACEA+PMSF is worthy of recommendation for further clinical settings. Pharmacokinetic interactions of ACEA+PMSF with ethosuximide and valproate seem to be responsible for a significant suppression of PTZ-induced seizures in mice. The combination of ACEA+PMSF with clonazepam seems to be neutral from a preclinical viewpoint.
journal_name
Prog Neuropsychopharmacol Biol Psychiatryauthors
Andres-Mach M,Zolkowska D,Barcicka-Klosowska B,Haratym-Maj A,Florek-Luszczki M,Luszczki JJdoi
10.1016/j.pnpbp.2012.07.001subject
Has Abstractpub_date
2012-12-03 00:00:00pages
301-9issue
2eissn
0278-5846issn
1878-4216pii
S0278-5846(12)00160-1journal_volume
39pub_type
杂志文章abstract::1. The effect of chronic antidepressant administration on CRE-, SP1- and GRE-binding activity was studied in rat hippocampus and frontal cortex. 2. Fluoxetine and desipramine (3 and 10 mg/kg/day respectively) were given to rats for 21 consecutive days. The animals were killed 3 hr after the last injection and nuclear ...
journal_title:Progress in neuro-psychopharmacology & biological psychiatry
pub_type: 杂志文章
doi:10.1016/s0278-5846(98)00040-2
更新日期:1998-07-01 00:00:00
abstract::A common approach to study neuronal aspects of emotional reactivity of borderline personality disorder (BPD) is to study the brain response to emotional faces with functional magnetic resonance imaging (fMRI). 10 BPD patients and 10 matched controls were submitted to an emotional discrimination task in which subjects ...
journal_title:Progress in neuro-psychopharmacology & biological psychiatry
pub_type: 杂志文章
doi:10.1016/j.pnpbp.2009.08.022
更新日期:2009-11-13 00:00:00
abstract::1. The plasma concentrations of unconjugated phenylacetic acid and m-hydroxyphenylacetic acid are lower in male than in female subjects. 2. The plasma concentrations of unconjugated phenylacetic acid and mandelic acid decrease with increasing weight and height for all subjects combined. The same relationships apply fo...
journal_title:Progress in neuro-psychopharmacology & biological psychiatry
pub_type: 杂志文章
doi:10.1016/0278-5846(91)90025-v
更新日期:1991-01-01 00:00:00
abstract::The present study investigated the effect of monoamine oxidase inhibitors, nialamide which is a non specific monoamine oxidase inhibitor (MAOI), toloxatone which is a A type MAOI and L-deprenyl which is a B type MAOI compared with classical tricyclic antidepressants (clomipramine, desipramine and imipramine), on the e...
journal_title:Progress in neuro-psychopharmacology & biological psychiatry
pub_type: 杂志文章
doi:10.1016/0278-5846(87)90026-1
更新日期:1987-01-01 00:00:00
abstract::1. A randomized, placebo controlled, double-blind cross-over study was conducted to evaluate the clinical efficacy of the anticholinergic agent, benztropine mesylate (CogentinR) in 29 patients with mild to moderate, idiopathic Parkinson disease. 2. Patients were maintained on a stable, therapeutically optimal dosage a...
journal_title:Progress in neuro-psychopharmacology & biological psychiatry
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1016/s0364-7722(82)80107-0
更新日期:1982-01-01 00:00:00
abstract::The aim of the present study was to evaluate the putative antidepressive and cognitive enhancer effects of phosphatidylserine (BC-PS). The antidepressive effect of BC-PS (50, 100 or 200 mg/kg), compared to saline or imipramine (IMI; 25 mg/kg), was studied in the forced swimming test in rats. These drugs were administe...
journal_title:Progress in neuro-psychopharmacology & biological psychiatry
pub_type: 杂志文章
doi:10.1016/j.pnpbp.2004.05.013
更新日期:2004-07-01 00:00:00
abstract::Cocaine use disorders are an unrelenting public health concern. Behavioral treatments reduce cocaine use by providing non-drug alternative reinforcers. The purpose of this human laboratory experiment was to determine how response cost for non-drug alternative reinforcers influenced cocaine choice. Seven cocaine-using,...
journal_title:Progress in neuro-psychopharmacology & biological psychiatry
pub_type: 杂志文章
doi:10.1016/j.pnpbp.2011.10.003
更新日期:2012-01-10 00:00:00
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journal_title:Progress in neuro-psychopharmacology & biological psychiatry
pub_type: 杂志文章,评审
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更新日期:2016-08-01 00:00:00
abstract::1. Clinical data suggest that valproate (VPA) may be useful in prophylaxis of affective disorders, which show disturbances of the serotoninergic system. On the other hand, chronic stress has an adverse effect on affective disorders, those with disturbances of the serotonergic system, especially. 2. In order to study t...
journal_title:Progress in neuro-psychopharmacology & biological psychiatry
pub_type: 杂志文章
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更新日期:1993-03-01 00:00:00
abstract::1. As part of a systematic investigation of the effects of lithium administration on neuroendocrine function we investigated the luteinizing hormone (LH) response to luteinizing hormone releasing hormone (LHRH) of healthy males. 2. In healthy volunteers after 3 weeks of therapeutic doses of lithium the LH response to ...
journal_title:Progress in neuro-psychopharmacology & biological psychiatry
pub_type: 杂志文章
doi:10.1016/0278-5846(88)90043-7
更新日期:1988-01-01 00:00:00
abstract::Although ECT is a highly effective treatment for severe depression and other psychiatric syndromes, its mode of action is not known. Recent studies have suggested that effects of ECT on central neurotransmitter receptors may underlie its therapeutic action. The effects of chronically administered electroconvulsive sho...
journal_title:Progress in neuro-psychopharmacology & biological psychiatry
pub_type: 杂志文章
doi:10.1016/0278-5846(83)90120-3
更新日期:1983-01-01 00:00:00
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journal_title:Progress in neuro-psychopharmacology & biological psychiatry
pub_type: 杂志文章
doi:10.1016/0278-5846(90)90025-c
更新日期:1990-01-01 00:00:00
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journal_title:Progress in neuro-psychopharmacology & biological psychiatry
pub_type: 杂志文章
doi:10.1016/j.pnpbp.2011.02.006
更新日期:2011-07-01 00:00:00
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journal_title:Progress in neuro-psychopharmacology & biological psychiatry
pub_type: 杂志文章
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更新日期:2015-04-03 00:00:00
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journal_title:Progress in neuro-psychopharmacology & biological psychiatry
pub_type: 杂志文章
doi:10.1016/j.pnpbp.2006.12.014
更新日期:2007-04-13 00:00:00
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journal_title:Progress in neuro-psychopharmacology & biological psychiatry
pub_type: 临床试验,杂志文章,随机对照试验
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更新日期:1996-08-01 00:00:00
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journal_title:Progress in neuro-psychopharmacology & biological psychiatry
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journal_title:Progress in neuro-psychopharmacology & biological psychiatry
pub_type: 临床试验,杂志文章
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journal_title:Progress in neuro-psychopharmacology & biological psychiatry
pub_type: 杂志文章
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journal_title:Progress in neuro-psychopharmacology & biological psychiatry
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更新日期:2016-01-04 00:00:00
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journal_title:Progress in neuro-psychopharmacology & biological psychiatry
pub_type: 杂志文章
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journal_title:Progress in neuro-psychopharmacology & biological psychiatry
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doi:10.1016/j.pnpbp.2007.04.014
更新日期:2007-08-15 00:00:00
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journal_title:Progress in neuro-psychopharmacology & biological psychiatry
pub_type: 杂志文章
doi:10.1016/s0278-5846(82)80187-5
更新日期:1982-01-01 00:00:00
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journal_title:Progress in neuro-psychopharmacology & biological psychiatry
pub_type: 杂志文章
doi:10.1016/j.pnpbp.2013.11.005
更新日期:2014-03-03 00:00:00
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journal_title:Progress in neuro-psychopharmacology & biological psychiatry
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doi:10.1016/j.pnpbp.2006.03.018
更新日期:2006-09-30 00:00:00
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journal_title:Progress in neuro-psychopharmacology & biological psychiatry
pub_type: 杂志文章
doi:10.1016/0278-5846(86)90073-4
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journal_title:Progress in neuro-psychopharmacology & biological psychiatry
pub_type: 杂志文章
doi:10.1016/j.pnpbp.2008.08.004
更新日期:2008-12-12 00:00:00
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journal_title:Progress in neuro-psychopharmacology & biological psychiatry
pub_type: 杂志文章,评审
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更新日期:2018-12-20 00:00:00
abstract::1. Alzheimer's Disease (AD) is accompanied by a disruption in iron metabolism. There is no universally accepted method for detecting brain iron. 2. The authors have developed a novel "ratio" method which uses the red nucleus as an internal reference. We postulated that this method would improve our sensitivity in dete...
journal_title:Progress in neuro-psychopharmacology & biological psychiatry
pub_type: 临床试验,杂志文章
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更新日期:1997-11-01 00:00:00