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1-Methyl-1,2,3,4-tetrahydroisoquinoline enhances the anticonvulsant action of carbamazepine and valproate in the mouse maximal electroshock seizure model.
Neuropharmacology. 2006 Feb; 50(2):133-42.N

Abstract

1-Methyl-1,2,3,4-tetrahydroisoquinoline (1-MeTHIQ - an endogenous parkinsonism-preventing substance) administered intraperitoneally at a dose of 20 mg/kg considerably elevated the threshold for electroconvulsions in mice from 6.4 to 8.4 mA (P < 0.05). In contrast, the agent administered at 5 and 10 mg/kg had no significant impact on the electroconvulsive threshold in mice. Moreover, 1-MeTHIQ (at a subthreshold dose of 10 mg/kg) potentiated the anticonvulsant action of valproate (VPA) against maximal electroshock (MES)-induced seizures in mice, reducing its median effective dose (ED50) from 232 to 170 mg/kg (P < 0.001). Similarly, 1-MeTHIQ (at 10 mg/kg) enhanced the antielectroshock activity of carbamazepine (CBZ) in mice, decreasing its ED50 from 10.8 to 7.8 mg/kg (P < 0.05). In contrast, 1-MeTHIQ (at 10 mg/kg) did not affect the anticonvulsant action of phenytoin and phenobarbital against MES-induced seizures in mice. The evaluation of acute neurotoxic effects of the studied antiepileptic drugs (AEDs) in combination with 1-MeTHIQ, as regards motor coordination impairment in the chimney test, revealed no significant changes in median toxic doses (TD50) of conventional AEDs after systemic administration of 1-MeTHIQ (up to 10 mg/kg). Pharmacokinetic characterization of interactions between 1-MeTHIQ (10 mg/kg) and VPA (170 mg/kg) or CBZ (7.8 mg/kg) revealed no significant changes in total brain concentrations of CBZ and VPA, indicating that the observed enhancement of antiseizure effects of CBZ and VPA by 1-MeTHIQ was pharmacodynamic in nature. Based on our preclinical study, it may be concluded that 1-MeTHIQ exerts the anticonvulsant effects increasing the threshold for electroconvulsions and potentiating the antiseizure action of CBZ and VPA against maximal electroshock. The antiseizure properties of 1-MeTHIQ (an endogenous parkinsonism-preventing substance) and its exact physiological role in the brain need extensive examination in further neuropharmacological studies.

Authors+Show Affiliations

Department of Pathophysiology, Medical University of Lublin, Jaczewskiego 8, 20-090 Lublin, Poland. jluszczki@yahoo.comNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16153667

Citation

Luszczki, Jarogniew J., et al. "1-Methyl-1,2,3,4-tetrahydroisoquinoline Enhances the Anticonvulsant Action of Carbamazepine and Valproate in the Mouse Maximal Electroshock Seizure Model." Neuropharmacology, vol. 50, no. 2, 2006, pp. 133-42.
Luszczki JJ, Antkiewicz-Michaluk L, Czuczwar SJ. 1-Methyl-1,2,3,4-tetrahydroisoquinoline enhances the anticonvulsant action of carbamazepine and valproate in the mouse maximal electroshock seizure model. Neuropharmacology. 2006;50(2):133-42.
Luszczki, J. J., Antkiewicz-Michaluk, L., & Czuczwar, S. J. (2006). 1-Methyl-1,2,3,4-tetrahydroisoquinoline enhances the anticonvulsant action of carbamazepine and valproate in the mouse maximal electroshock seizure model. Neuropharmacology, 50(2), 133-42.
Luszczki JJ, Antkiewicz-Michaluk L, Czuczwar SJ. 1-Methyl-1,2,3,4-tetrahydroisoquinoline Enhances the Anticonvulsant Action of Carbamazepine and Valproate in the Mouse Maximal Electroshock Seizure Model. Neuropharmacology. 2006;50(2):133-42. PubMed PMID: 16153667.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 1-Methyl-1,2,3,4-tetrahydroisoquinoline enhances the anticonvulsant action of carbamazepine and valproate in the mouse maximal electroshock seizure model. AU - Luszczki,Jarogniew J, AU - Antkiewicz-Michaluk,Lucyna, AU - Czuczwar,Stanislaw J, Y1 - 2005/09/08/ PY - 2005/05/24/received PY - 2005/07/12/revised PY - 2005/07/22/accepted PY - 2005/9/13/pubmed PY - 2006/4/13/medline PY - 2005/9/13/entrez SP - 133 EP - 42 JF - Neuropharmacology JO - Neuropharmacology VL - 50 IS - 2 N2 - 1-Methyl-1,2,3,4-tetrahydroisoquinoline (1-MeTHIQ - an endogenous parkinsonism-preventing substance) administered intraperitoneally at a dose of 20 mg/kg considerably elevated the threshold for electroconvulsions in mice from 6.4 to 8.4 mA (P < 0.05). In contrast, the agent administered at 5 and 10 mg/kg had no significant impact on the electroconvulsive threshold in mice. Moreover, 1-MeTHIQ (at a subthreshold dose of 10 mg/kg) potentiated the anticonvulsant action of valproate (VPA) against maximal electroshock (MES)-induced seizures in mice, reducing its median effective dose (ED50) from 232 to 170 mg/kg (P < 0.001). Similarly, 1-MeTHIQ (at 10 mg/kg) enhanced the antielectroshock activity of carbamazepine (CBZ) in mice, decreasing its ED50 from 10.8 to 7.8 mg/kg (P < 0.05). In contrast, 1-MeTHIQ (at 10 mg/kg) did not affect the anticonvulsant action of phenytoin and phenobarbital against MES-induced seizures in mice. The evaluation of acute neurotoxic effects of the studied antiepileptic drugs (AEDs) in combination with 1-MeTHIQ, as regards motor coordination impairment in the chimney test, revealed no significant changes in median toxic doses (TD50) of conventional AEDs after systemic administration of 1-MeTHIQ (up to 10 mg/kg). Pharmacokinetic characterization of interactions between 1-MeTHIQ (10 mg/kg) and VPA (170 mg/kg) or CBZ (7.8 mg/kg) revealed no significant changes in total brain concentrations of CBZ and VPA, indicating that the observed enhancement of antiseizure effects of CBZ and VPA by 1-MeTHIQ was pharmacodynamic in nature. Based on our preclinical study, it may be concluded that 1-MeTHIQ exerts the anticonvulsant effects increasing the threshold for electroconvulsions and potentiating the antiseizure action of CBZ and VPA against maximal electroshock. The antiseizure properties of 1-MeTHIQ (an endogenous parkinsonism-preventing substance) and its exact physiological role in the brain need extensive examination in further neuropharmacological studies. SN - 0028-3908 UR - https://www.unboundmedicine.com/medline/citation/16153667/1_Methyl_1234_tetrahydroisoquinoline_enhances_the_anticonvulsant_action_of_carbamazepine_and_valproate_in_the_mouse_maximal_electroshock_seizure_model_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0028-3908(05)00287-X DB - PRIME DP - Unbound Medicine ER -