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Effect of dextromethorphan/quinidine on pentylenetetrazole- induced clonic and tonic seizure thresholds in mice.
Neurosci Lett. 2020 Jun 11; 729:134988.NL

Abstract

INTRODUCTION

This study aimed to investigate the effects of dextromethorphan (DM) or dextromethorphan/quinidine (DM/Q) against pentylenetetrazole (PTZ)- induced seizure threshold in mice and the probable involvement of N-methyl d-aspartate (NMDA), sigma-1 and serotonin 1A (5-HT1A) receptors.

MATERIAL AND METHODS

NMRI male mice (25-30 g) received quinidine (10, 20, and 30 mg/kg), DM (5, 10, 25, and 50 mg/kg) or DM/Q (10/20, 25/20, and 50/20 mg/kg), 30 min before the infusion of PTZ. ketamine (1 and 5 mg/kg), BD-1047 (2.5 and 5 mg/kg) or WAY-100635 (0.5 and 1 mg/kg) were administrated as pre-treatment 30 min before the selected dose of DM/Q. Seizures were induced by intravenous PTZ infusion. All data were presented as means ± S.E.M. One-way ANOVA test was used to determine statistical significance (p < 0.05).

RESULTS

DM (25 and 50 mg/kg) significantly increased PTZ- induced seizure threshold. DM/Q at doses of 10/20 and 25/20 mg/kg had anticonvulsant effect, while at a dose of 50/20 mg/kg attenuated anticonvulsant effect of DM 50 mg/kg. Ketamine (5 mg/kg) or WAY-100635 (1 mg/kg) potentiated, while BD-1047 (2.5 and 5 mg/kg) attenuated the anticonvulsant effect of DM/Q 10/20 mg/kg.

CONCLUSION

The results of present study demonstrate that combination with quinidine potentiates the anticonvulsant effect of DM at lower doses, while attenuates it at higher dose. Meanwhile, the effects of DM/Q on seizure activity likely involve an interaction with NMDA, the sigma-1 or the 5-HT1A receptor which may be secondary to the elevation of DM levels.

Authors+Show Affiliations

Physiology Research Center, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, Iran. Electronic address: hassanjamali342@gmail.com.Physiology Research Center, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, Iran; Department of Physiology, Faculty of Medicine, Kashan University of Medical Sciences, Kashan, Iran. Electronic address: heydariazh@gmail.com.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32325102

Citation

Jamali, Hassan, and Azhdar Heydari. "Effect of Dextromethorphan/quinidine On Pentylenetetrazole- Induced Clonic and Tonic Seizure Thresholds in Mice." Neuroscience Letters, vol. 729, 2020, p. 134988.
Jamali H, Heydari A. Effect of dextromethorphan/quinidine on pentylenetetrazole- induced clonic and tonic seizure thresholds in mice. Neurosci Lett. 2020;729:134988.
Jamali, H., & Heydari, A. (2020). Effect of dextromethorphan/quinidine on pentylenetetrazole- induced clonic and tonic seizure thresholds in mice. Neuroscience Letters, 729, 134988. https://doi.org/10.1016/j.neulet.2020.134988
Jamali H, Heydari A. Effect of Dextromethorphan/quinidine On Pentylenetetrazole- Induced Clonic and Tonic Seizure Thresholds in Mice. Neurosci Lett. 2020 Jun 11;729:134988. PubMed PMID: 32325102.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effect of dextromethorphan/quinidine on pentylenetetrazole- induced clonic and tonic seizure thresholds in mice. AU - Jamali,Hassan, AU - Heydari,Azhdar, Y1 - 2020/04/20/ PY - 2019/12/09/received PY - 2020/03/07/revised PY - 2020/04/13/accepted PY - 2020/4/24/pubmed PY - 2020/4/24/medline PY - 2020/4/24/entrez KW - Dextromethorphan KW - N-methyl-d-aspartate KW - Quinidine KW - Serotonin- 1A receptor KW - Sigma-1 receptor SP - 134988 EP - 134988 JF - Neuroscience letters JO - Neurosci. Lett. VL - 729 N2 - INTRODUCTION: This study aimed to investigate the effects of dextromethorphan (DM) or dextromethorphan/quinidine (DM/Q) against pentylenetetrazole (PTZ)- induced seizure threshold in mice and the probable involvement of N-methyl d-aspartate (NMDA), sigma-1 and serotonin 1A (5-HT1A) receptors. MATERIAL AND METHODS: NMRI male mice (25-30 g) received quinidine (10, 20, and 30 mg/kg), DM (5, 10, 25, and 50 mg/kg) or DM/Q (10/20, 25/20, and 50/20 mg/kg), 30 min before the infusion of PTZ. ketamine (1 and 5 mg/kg), BD-1047 (2.5 and 5 mg/kg) or WAY-100635 (0.5 and 1 mg/kg) were administrated as pre-treatment 30 min before the selected dose of DM/Q. Seizures were induced by intravenous PTZ infusion. All data were presented as means ± S.E.M. One-way ANOVA test was used to determine statistical significance (p < 0.05). RESULTS: DM (25 and 50 mg/kg) significantly increased PTZ- induced seizure threshold. DM/Q at doses of 10/20 and 25/20 mg/kg had anticonvulsant effect, while at a dose of 50/20 mg/kg attenuated anticonvulsant effect of DM 50 mg/kg. Ketamine (5 mg/kg) or WAY-100635 (1 mg/kg) potentiated, while BD-1047 (2.5 and 5 mg/kg) attenuated the anticonvulsant effect of DM/Q 10/20 mg/kg. CONCLUSION: The results of present study demonstrate that combination with quinidine potentiates the anticonvulsant effect of DM at lower doses, while attenuates it at higher dose. Meanwhile, the effects of DM/Q on seizure activity likely involve an interaction with NMDA, the sigma-1 or the 5-HT1A receptor which may be secondary to the elevation of DM levels. SN - 1872-7972 UR - https://www.unboundmedicine.com/medline/citation/32325102/Effect_of_dextromethorphan/quinidine_on_pentylenetetrazole-_induced_clonic_and_tonic_seizure_thresholds_in_mice L2 - https://linkinghub.elsevier.com/retrieve/pii/S0304-3940(20)30258-5 DB - PRIME DP - Unbound Medicine ER -
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