Table 1.

Central nervous system channelopathies.

Disease	Gene (protein)	Pharmacotherapy	Pharmacological perspectives
Epileptic syndromes including GEFS+, SMEI, BFNIS, BFNC, MPSI, ADNFLE, MLC, absence epilepsy and other epileptic encephalopathies (see text for abbreviations)	SCN1A (Nav1.1) SCN2A (Nav1.2) SCN3A (Nav1.3) SCN8A (Nav1.6) SCN1B (Nav2.1) KCNA1 (Kv1.1) KCNA2 (Kv1.2) KCNC3 (Kv3.3) KCND2 (Kv4.2) KCND3 (Kv4.3) KCNQ2 (Kv7.2) KCNQ3 (Kv7.3) KCNH5 (Kv10.1) KCNJ10 (Kir4.1) KCNJ11 (Kir6.2) ABCC8 (SUR1) KCNMA1 (KCa1.1) KCNT1 (KCa4.1) CACNA1C (Cav1.2) CACNA1A (Cav2.1) CACNA1H (Cav3.2) CLCN2 (ClC-2) GLIALCAM	Antiepileptic drugs aim at reducing neuronal hyperexcitability with different mechanisms: – Enhancement of GABAergic transmission: benzodiazepines, phenobarbital, valproate, stiripentol, topiramate – Inhibition of glutamatergic transmission: topiramate – Inhibition of Nav channels: phenytoin, carbamazepine, lamotrigine, valproate, topiramate, lacosamide, eslicarbazepine – Opening of K channels: retigabine, acetazolamide – Inhibition of T-type Cav channels: ethosuximide – Inhibition of the synaptic vescicle 2A: levetiracetam – Inhibition of presynaptic Cav2 channels α2δ auxiliary subunit: gabapentin, pregabalin – Inhibition of carbonic anhydrase: topiramate, acetazolamide	– Development of subtype-selective Nav channels ligands with improved safety and efficacy – Development of pharmacological chaperones for folding defective mutants of Nav, Kv and ClC channels – Development of more selective and safer Kv openers
Episodic and spinocerebellar ataxias	KCNA1 (Kv1.1) CACNA1A (Cav2.1) KCNC3 (Kv3.3) KCND3 (Kv4.3)	Symptomatic drugs aim at restoring cerebellar functioning and reducing frequency, duration and severity of attacks: – Inhibition of carbonic anhydrase: acetazolamide, in EA1 and EA2 – Inhibition of Kv channels: 4-aminopyridine, first choice in EA2 – Riluzole: Nav channels blocker and SK and TWIK channels opener, in cerebellar ataxias	– Opening of SK channels to restore Purkinje cells pacemaking: chlorzoxazone and 1-EBIO, in EA2 animal models – Kv1.1 dysinactivators
Familial hemiplegic migraine	CACNA1A (Cav2.1) SCN1A (Nav1.1)	Symptomatic and prophylactic drugs aim at reducing frequency and painful attacks: – Tricyclic antidepressants, β-blockers, triptans, Cav blockers, AEDs, acetazolamide	– Botulinum toxin