Metabotropic glutamate receptor 5 antagonist, MPEP, lacks anticonvulsant activity in acute models of epilepsy

Abstract

Abstract. Evaluation of the effects of different doses of 2-methyl-6-phenylethynyl-pyridine (MPEP), a selective antagonist of mGluR5, in acute models of epilepsy [pentylenetetrazole (PTZ) and maximal electroconvulsive shock (MES)], dosage relations and also whether if this effect is enhanced by conventional antiepileptic drugs. The anticonvulsant properties of MPEP were examined in mice who received MPEP by intracerebroventricular infusion prior to a subcutaneous injection of pentylenetetrazole and maximal electroshock. Evaluations of convulsive seizures caused by PTZ were performed by the loss of righting reflex while convulsive seizures caused by MES were performed by the occurence of tonic hind limb extension in adult mice. There was no significant difference in both groups (PTZ, MES) when compared with the control group. The present results do not support a significant anticonvulsant potential of MPEP on adult mice as a selective antagonist of mGluR5 in convulsive seizures.

Key words: metabotropic glutamate receptor 5, 2-methyl-6-phenylethynyl-pyridine, convulsive seizures

Keywords

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References

1. Havanka-Kanniainen H. Autonomic dysfunction in migraine with special reference to cardiovascular reflexes, plasma noradrenaline levels and effects of nimodipine [Doctoral dissertation]. 1986; Oulu: University of Oulu.
2. Sacks O. The physiological organisation of migraines. In: Migraine: Revised and Expanded. London: Picador, 1995; pp 193-204.
3. Cortelli P, de Carolis P, Sturani A, Ligabue A, et al. Cardiovascular and biochemical assessment in migraine patients submitted to tilt test. Funct Neurol 1986;1: 285-29.
4. Havanka-Kanniainen H, Tolonen U, Myllyla VV. Cardiovascular reflexes in young migraine patients. Headache 1986;41: 420-424.
5. Anthony M. Biochemical indices of sympathetic activity in migraine. Cephalalgia 1981;41: 83-89.
6. Boccuni M, Alessandri M, Fusco BM, Cang F. The pressor hyperresponsiveness to phenylephrine unmasks sympathetic hypofunction in migraine. Cephalalgia 1989;41: 239-245.
7. Cortelli P, Pierangeli G, Parch´y P, Contin M, Baruzzi A, Lugaresi E. Autonomic nervous system function in migraine without aura. Headache 1991;41: 457-462.
8. Gotoh F, Komatsumoto S, Araki N, Gomi S. Noradrenergic nervous activity in migraine. Arch Neurol 1984;41: 951-955.

9. Havanka-Kanniainen H, Juujarvi K, Tolonen U, Myllyla VV. Cardiovascular reflex and plasma noradrenaline levels in migraine patients before and during nimodipine medication. Headache 1987; 41: 34- 44.
10. Havanka-Kanniainen H, Tolonen U, Myllyla VV. Autonomic dysfunction in migraine: A survey of 188 patients. Headache 1988; 41: 465-470.
11. Shechter A, Stewart WF, Silberstein SD, Lipton RB. Migraine and autonomic nervous system function: a population-based, case-control study. Neurology 2002;58: 422-427.
12. Yakinci C, Mungen B, Er H, Durmaz Y & Karabüber H. Autonomic nervous system function in childhood migraine. Pediatrics International 1999;41: 529-533.
13. Hilsted J, Jensen SB. A simple test for autonomic neuropathy in juvenile diabetics. Acta Med Scand 1979;205: 385- 387.
14. Persson A, Solders G. R-R variations: a test of autonomic dysfunction. Acta Neurol Scand 1983; 67: 285-293.
15. Shahani TB, Day TJ, Cros D, Khalil N, Kneebone CS. RR interval variation and the sympathetic skin response in the assessment of autonomic function in peripheral neuropathy. Arch Neurol 1990;47: 659-664.
16. Headache Classification Committee of the International Headache Society. Classification and diagnostic criteria for headache disorders, cranial neuralgias and facial pain. Cephalalgia 1988;8: 1-96.
17. Yoldas T, Ulvi H, Dolu Y, Yigiter Y & Mungen B. RR interval variation and the sympathetic skin response in the assessment of autonomic function in migraine patients. Cephalalgia 2002;22: 1–35.
18. Sharma KR, Romano JG, Ram Ayyar D, Rotta FT, Facca A, Sanchez-Ramos J. Sympathetic skin response and heart rate variability in patients with Huntington disease. Arch Neurol 1999;56: 1248-1252.
19. Drory VE, Nisipeanu PF, Korczyn AD. Tests of autonomic dysfunction in patients with multiple sclerosis. Acta Neurol Scand 1995;92: 356-360.
20. Wang SJ, Fuh JL, Shan DE, Liao KK, Lin KP, Tsai CP, Wu ZA. Sympathetic skin response and R-R interval variation in Parkinson’s disease. Mov Disord 1993;8: 151-157.
21. Eckberg DL. Human sinus arrhythmia as an index of vagal cardiac outflow. J Appl Physiol 1983;54: 961- 966.
22. Low PA. Quantitation of autonomic dysfunction. In: Dyck PJ, Thomas PK (eds) Peripheral neuropathy. Saunders, Philadelphia, 1993, pp 729-745.
23. Low PA, Denq JC, Opher-Gehrking TL, Dyck PJ, O’Brien PC, Slezak JM. Effect of age and gender on sudomotor and cardiovagal function and blood pressure response to tilt in normal subjects. Muscle Nerve 1997;20: 1561-1568.
24. Apel S, Kuritzky A, Zahavi I, Zingelman M, Akselrod S. Evidence for instability of the autonomic nervous system in patients with migraine headache. Headache 1992;32: 10-17.
25. Tabata M, Takeshima T, Burioka N, Nomura T, Ishizaki K, Mori N, Kowa H, Nakashima K. Cosinor analysis of heart rate variability in ambulatory migraineurs. Headache 2000;40: 457-463.
26. Thomsen LL, Iversen HK, Boesen F, Olesen J. Transcranial Doppler and cardiovascular responses during cardiovascular autonomic tests in migraineurs during and outside attacks. Brain 1995;118: 1319- 1327.
27. Lance JW. Current concepts of migraine pathogenesis. Neurology 1993;41: 11-15.
28. Pearce JMS. Neural aspects of migraine. In: Blau JN (Ed) Migraine: Clinical and Research Aspects. The Johns Hopkins University Press, Baltimore, 1987, pp 247-264.
29. Adams RD, Victor M, Ropper AH. Principles of Neurology, 6th edn. McGraw-Hill Inc., New York, 1997, pp 522- 51.