[Home ] [Archive]   [ فارسی ]  
:: Main :: About :: Current Issue :: Archive :: Search :: Submit :: Contact ::
:: ::
Back to the articles list Back to browse issues page
Effect of acute administration of quinidine, dextromethorphan and combination of dextromethorphan/quinidine on pentylenetetrazole (PTZ)-induced clonic and tonic seizure thresholds in mice
Hassan Jamali , Azhdar Heydari *
Physiology Research Center, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, I.R. Iran. , heydariazh@gmail.com
Abstract:   (156 Views)
Background: Dextromethorphan (DM) as a non-opioid Anti-cough has neuroprotective effects. Combination of DM with quinidine decreases rapid metabolism of DM to dextrorphan (DX). This study aimed to investigate the effects of acute administration of quinidine, DM and combination of dextromethorphan/quinidine (DM/Q) on pentylenetetrazole (PTZ)-induced clonic and tonic seizure thresholds in mice.
Materials and Methods: A total of 84 male mice of the NMRI strain (20-25 g, n=7 in each group) were used in this study. Different doses of DM (5, 10, 25 and 50 mg/kg), quinidine (10, 20, and 30 mg/kg) and DM/Q (5/20, 10/20, 25/20, and 50/20 mg/kg) were intraperitoneally administrated 30 min before the seizure induction. Intravenous infusion of PTZ was used to induce seizure induction and latencies to the occurrence of general clonus and tonic hind limb extension were recorded and converted to the seizure threshold dose.
Results: Quinidine at dose of 30 mg/kg significantly increased the threshold of tonic seizure (P<0.05). DM at doses of 25 and 50 mg/kg significantly increased threshold of clonic (P<0.05) and tonic (P<0.001) seizures. DM/Q at dose of 50/20 mg/kg significantly decreased the threshold of clonic and tonic seizures (P<0.001).
Conclusion:  According to the findings of this study, different effect of DM on clonic and tonic seizure thresholds may represent the different sensitivity of forebrain and hindbrain seizure circuitry to DM. Also, decreased effect of DM in the presence of quinidine may also be due to a change in the metabolism of DM.
Keywords: Dextromethorphan, Quinidine, Pentylenetetrazole, Seizure, Mice
     
Type of Study: Research | Subject: medicine, paraclinic
Received: 2019/02/13 | Accepted: 2019/05/18
References
1. Bell GS, Sander JW. The epidemiology of epilepsy: The size of the problem. Seizure 2001; 10(4): 306-16.
2. Hitiris N, Brodie MJ. Modern antiepileptic drugs: guidelines and beyond. Curr Opin Neurol 2006; 19(2): 175-80.
3. Romanelli F, Smith KM. Dextromethorphan abuse: clinical effects and management. J Am Pharm Assoc 2009; 49(2): e20-e7.
4. Pu B, Xue Y, Wang Q, Hua C, Li X. Dextromethorphan provides neuroprotection via anti-inflammatory and anti-excitotoxicity effects in the cortex following traumatic brain injury. Mol Med Rep 2015; 12(3): 3704-10.
5. Mousavi SA, Saadatnia M, Khorvash F, Hoseini T, Sariaslani P. Evaluation of the neuroprotective effect of dextromethorphan in the acute phase of ischaemic stroke. Arch Med Sci 2011; 7(3): 465-9.
6. King MR, Ladha KS, Gelineau AM, Anderson TA. Perioperative Dextromethorphan as an Adjunct for Postoperative Pain: A Meta-analysis of Randomized Controlled Trials. Anesthesiology 2016; 124(3): 696-705.
7. Chien YH, Lin MI, Weng WC, Du JC, Lee WT. Dextromethorphan in the treatment of early myoclonic encephalopathy evolving into migrating partial seizures in infancy. J Formos Med Assoc 2012; 111(5): 290-4.
8. Schmid B, Bircher J, Preisig R, Küpfer A. Polymorphic dextromethorphan metabolism: co‐segregation of oxidative O‐demethylation with debrisoquin hydroxylation. Clin Pharmacol Therapeutics 1985; 38(6): 618-24.
9. Nguyen L, Thomas KL, Lucke-Wold BP, Cavendish JZ, Crowe MS, Matsumoto RR. Dextromethorphan: An update on its utility for neurological and neuropsychiatric disorders. Pharmacol Therapeutics 2016; 159: 1-22.
10. Taylor CP, Traynelis SF, Siffert J, Pope LE, Matsumoto RR. Pharmacology of dextromethorphan: Relevance to dextromethorphan/quinidine (Nuedexta®) clinical use. Pharmacol Therapeutics 2016; 170: 82-164.
11. Werling LL, Keller A, Frank JG, Nuwayhid SJ. A comparison of the binding profiles of dextromethorphan, memantine, fluoxetine and amitriptyline: treatment of involuntary emotional expression disorder. Experimental Neurol 2007; 207(2): 248-57.
12. Nguyen L, Robson MJ, Healy JR, Scandinaro AL, Matsumoto RR. Involvement of sigma-1 receptors in the antidepressant-like effects of dextromethorphan. PloS One 2014; 9(2): e89985.
13. [13] Netzer R, Pflimlin P, Trube G. Dextromethorphan blocks N-methyl-D-aspartate-induced currents and voltage-operated inward currents in cultured cortical neurons. European J Pharmacol 1993; 238(2-3): 209-16.
14. Franklin PH, Murray TF. High affinity [3H] dextrorphan binding in rat brain is localized to a noncompetitive antagonist site of the activated N-methyl-D-aspartate receptor-cation channel. Molecular Pharmacol 1992; 41(1): 134-46.
15. Ferkany JW, Borosky SA, Clissold DB, Pontecorvo MJ. Dextromethorphan inhibits NMDA-induced convulsions. European J Pharmacol 1988; 151(1): 151-4.
16. Laroia N, McBride L, Baggs R, Guillet R. Dextromethorphan ameliorates effects of neonatal hypoxia on brain morphology and seizure threshold in rats. Developmental Brain Res 1997; 100(1): 29-34.
17. Mohseni G, Ostadhadi S, Akbarian R, Chamanara M, Norouzi-Javidan A, Dehpour AR. Anticonvulsant effect of dextrometrophan on pentylenetetrazole-induced seizures in mice: Involvement of nitric oxide and N-methyl-d-aspartate receptors. Epilepsy Behav 2016; 65: 49-55.
18. Kim HC, Ko KH, Kim WK, Shin EJ, Kang KS, Shin CY, et al. Effects of dextromethorphan on the seizures induced by kainate and the calcium channel agonist BAY k-8644: comparison with the effects of dextrorphan. Behav Brain Res 120(2): 169-75.
19. Kim HC, Shin CY, Seo DO, Jhoo JH, Jhoo WK, Kim WK, et al. New morphinan derivatives with negligible psychotropic effects attenuate convulsions induced by maximal electroshock in mice. Life Sci 2003; 72(16): 1883-95.
20. Feeser HR, Kadis JL, Prince DA. Dextromethorphan, a common antitussive, reduces kindled amygdala seizures in the rat. Neurosci Lett 1988; 86(3): 340-5.
21. Tran HQ, Chung YH, Shin EJ, Tran TV, Jeong JH, Jang CG, et al. MK-801, but not naloxone, attenuates high-dose dextromethorphan-induced convulsive behavior: possible involvement of the GluN2B receptor. Toxicol Appl Pharmacol 2017; 334: 158-66.
22. Takazawa A, Anderson P, Abraham WC. Effects of dextromethorphan, a nonopioid antitussive, on development and expression of amygdaloid kindled seizures. Epilepsia 1990; 31(5): 496-502.
23. Löscher W, Hönack D. Differences in anticonvulsant potency and adverse effects between dextromethorphan and dextrorphan in amygdala-kindled and non-kindled rats. Eur J Pharmacol 1993; 238(2-3): 191-200.
24. Thompson KW, Wasterlain CG. Dextromethorphan and its combination with phenytoin facilitate kindling. Neurology 1993; 43(5): 992-4.
25. Kim HC, Bing G, Jhoo WK, Kim WK, Shin EJ, Im DH, et al. Metabolism to dextrorphan is not essential for dextromethorphan's anticonvulsant activity against kainate in mice. Life Sci 2003; 72(7): 769-83.
26. Shin EJ, Nah SY, Kim WK, Ko KH, Jhoo WK, Lim YK, et al. The dextromethorphan analog dimemorfan attenuates kainate‐induced seizures via σ1 receptor activation: comparison with the effects of dextromethorphan. British J Pharmacol 2005; 144(7): 908-18.
27. Shin EJ, Nah SY, Chae JS, Bing G, Shin SW, Yen TPH, et al. Dextromethorphan attenuates trimethyltin-induced neurotoxicity via σ1 receptor activation in rats. Neurochemistry Int 2007; 50(6): 791-9.
28. Gonda X. Basic pharmacology of NMDA receptors. Current Pharmaceutical Design 2012; 18(12): 1558-67.
29. Cole AE, Eccles CU, Aryanpur J, Fisher RS. Selective depression of N-methyl--aspartate-mediated responses by dextrorphan in the hippocampal slice in rat. Neuropharmacology 1989; 28(3): 249-54.
30. Chen HH, Chan MH. Developmental lead exposure differentially alters the susceptibility to chemoconvulsants in rats. Toxicology 2002; 173 (3): 249–57.
31. Mesdaghinia A, Yazdanpanah H, Seddighi M, Banafshe H, Heydari A. Effect of short-term lead exposure on PTZ-induced seizure threshold in mice. Toxicology Lett 2010; 199(1): 6-9.
32. Heydari A, Davoudi S. The effect of sertraline and 8-OH-DPAT on the PTZ_induced seizure threshold: Role of the nitrergic system. Seizure 2017; 45: 119-24.
33. Esmaili Z, Heydari A. Effect of acute caffeine administration on PTZ-induced seizure threshold in mice: Involvement of adenosine receptors and NO-cGMP signaling pathway. Epilepsy Res 2019; 149: 1-8.
34. Huang RQ, Bell-Horner CL, Dibas MI, Covey DF, Drewe JA, Dillon GH. Pentylenetetrazole-induced inhibition of recombinant γ-aminobutyric acid type A (GABAA) receptors: mechanism and site of action. J Pharmacol Experimental Therapeutics 2001; 298(3): 986-95.
35. Ronne-Engström E, Hillered L, Flink R, Spännare B, Ungerstedt U, Carlson H. Intracerebral microdialysis of extracellular amino acids in the human epileptic focus. J Cerebral Blood Flow Metabolism 1992; 12(5): 873-6.
36. During MJ, Spencer DD. Extracellular hippocampal glutamate and spontaneous seizure in the conscious human brain. Lancet 1993; 341(8861): 1607-10.
37. Ohi Y, Tsunekawa S, Haji A. Dextromethorphan inhibits the glutamatergic synaptic transmission in the nucleus tractus solitarius of guinea pigs. J Pharmacological Sci 2011; 116(1): 54-62.
38. Annels S, Ellis Y, Davies J. Non-opioid antitussives inhibit endogenous glutamate release from rabbit hippocampal slices. Brain Res 1991; 564(2): 341-3.
39. Cotton DB, Hallak M, Janusz C, Irtenkauf SM, Berman RF. Central anticonvulsant effects of magnesium sulfate on N-methyl-D-aspartate-induced seizures. Am J Obstetrics Gynecol 1993; 168(3): 974-8.
40. Freitas R, Sousa F, Viana G, Fonteles M. Effect of gabaergic, glutamatergic, antipsychotic and antidepressant drugs on pilocarpine-induced seizures and status epilepticus. Neurosci Lett 2006; 408(2): 79-83.
41. Sato K, Morimoto K, Okamoto M. Anticonvulsant action of a non-competitive antagonist of NMDA receptors (MK-801) in the kindling model of epilepsy. Brain Res 1988; 463(1): 12-20.
42. Gale K. Progression and generalization of seizure discharge: anatomical and neurochemical substrates. Epilepsia 1988; 29: S15-S34.
43. Su TP, Hayashi T, Maurice T, Buch S, Ruoho AE. The sigma-1 receptor chaperone as an inter-organelle signaling modulator. Trends Pharmacological Sci 2010; 31(12): 557-66.
44. Chu UB, Ruoho AE. Biochemical pharmacology of the sigma-1 receptor. Molecular Pharmacol 2016; 89(1): 142-53.
45. Matsumoto RR, Nguyen L, Kaushal N, Robson MJ. Sigma (σ) receptors as potential therapeutic targets to mitigate psychostimulant effects. Advances Pharmacol 2014; 69: 323-86.
46. Guo L, Chen Y, Zhao R, Wang G, Friedman E, Zhang A, et al. Allosteric modulation of sigma‐1 receptors elicits anti‐seizure activities. British J Pharmacol 2015; 172(16): 4052-65.
47. Vavers E, Svalbe B, Lauberte L, Stonans I, Misane I, Dambrova M, et al. The activity of selective sigma-1 receptor ligands in seizure models in vivo. Behav Brain Res 2017; 328: 13-8.
48. Guitart X, Codony X, Monroy X. Sigma receptors: biology and therapeutic potential. Psychopharmacology 2004; 174(3): 301-19.
49. Quirion R, Bowen WD, Itzhak Y, Junien JL, Musacchio J, Rothman RB, et al. A proposal for the classification of sigma binding sites. Trends Pharmacological Sci 1992; 13: 85-6.
Send email to the article author

Add your comments about this article
Your username or Email:

CAPTCHA


XML   Persian Abstract   Print



Back to the articles list Back to browse issues page
مجله علمی پژوهشی فیض ::: دانشگاه علوم پزشکی کاشان KAUMS Journal ( FEYZ )
Persian site map - English site map - Created in 0.05 seconds with 32 queries by YEKTAWEB 3921