Table 3.

Metabotropic glutamate receptors in seizure disorders.

Receptor	G protein	Recent studies and therapeutic outcomes	References
Group I mGluR1/5	Gq/11	Overexpressing mGluR1 increased seizure susceptibility in pilocarpine-treated adult male BL6SJ/F1 hybrid mice.	Pitsch et al., 2007
		Treatment with mGluR1 antagonist AIDA (up to 1 μmol/site, i.c.v.) inhibited, while treatment with group I mGluR agonist DHPG (up to 50 nmol/site, i.c.v.) exacerbated, seizures in PTZ-treated young male ICR mice in a dose-dependent manner.	Watanabe et al., 2011
		Selective mGluR5 negative allosteric modulator CTEP (2 mg/kg, p.o.) decreased, while mGluR5 positive allosteric modulator RO6807794 (0.3 mg/kg, i.p.) increased the hyperactivity and seizures in Tsc2-deficient male and female mice.	Kelly et al., 2018
		Positive modulation of mGluR5 by VU0360172 (50 mg/kg, i.p.) attenuated seizures induced by TMEV in young male C57BL/6 mice.	Hanak et al., 2019
		Conditional ablation of mGluR5 in astrocytes decreased the rate of glutamate clearance in the hippocampus during epileptogenesis of adult male and female mice.	Umpierre et al., 2019
Group II mGluR2/3	Gi/o	Activation of mGluR2/3 by selective agonists LY379268 and LY389795 (0.001-10 nmol, i.c.v. or 1-30 mg/kg, i.p.) suppressed the sound-triggered or mGluR1/5 agonist DHPG-induced clonic seizures in young male and female DBA/2 mice a dose-dependent manner.	Moldrich et al., 2001
		Activation of mGluR2/3 by LY379268 (0.33 or 1 mg/kg, i.p.) increased, while mGluR2/3 inhibition by LY341495 (0.33, 1 or 5 mg/kg, i.p.) decreased, the occurrence of SWDs in an adult male rat model of absence epilepsy in a dose-dependent manner.	Ngomba et al., 2005
		Treatment with mGluR2/3 agonist APDC (20 nmol/site, i.c.v.) inhibited, while treatment with group II mGluR antagonist EGLU (up to 200 nmol/site, i.c.v.) exacerbated, seizures in PTZ-treated young male ICR mice in a dose-dependent manner.	Watanabe et al., 2011
Group III mGluR4/6/7/8	Gi/o	Ablation of mGluR7 elevated excitability and increased susceptibility to tonic-clonic seizures induced by PTZ or bicuculline in mice.	Sansig et al., 2001
		Genetic deletion of mGluR4 increased the severity of pilocarpine-induced seizure in adult male CD-1 mice but did not alter the spontaneous recurrent seizures.	Pitsch et al., 2007
		Positive modulation of mGluR4 by allosteric ligand PHCCC (10 mg/kg, s.c.) enhanced absence-like seizures in Wistar Albino Glaxo/Rijswijk rats as well as the PTZ-treated adult male WAG/Rij and ACI mice.	Ngomba et al., 2008
		Treatment with mGluR4/8 agonist L-AP4 (up to 20 nmol/site, i.c.v.) inhibited, while treatment with group III mGluR antagonist MPPG (up to 50 nmol/site, i.c.v.) exacerbated, seizures in PTZ-treated young male ICR mice in a dose-dependent manner.	Watanabe et al., 2011
		Negative modulation of mGluR7 by allosteric inhibitor ADX71743 (100 mg/kg, i.p.) enhanced thalamic synaptic transmission and induced absence epileptic seizures and lethargy in male adult mice.	Tassin et al., 2016

Abbreviations: PTZ, pentylenetetrazol; SWD, spike and wave discharge; TMEV, Theiler’s murine encephalomyelitis virus; TSC, tuberous sclerosis complex.