Combination drug therapy for the treatment of status epilepticus

Abstract

Status epilepticus (SE) is a common neurological emergent disease with high mortality and disability rates. Rapidly and effectively controlling seizures is key to saving the lives of patients and improving their prognoses. Traditional antiepileptic drugs for SE are ineffective in 30-40% of cases. In light of the diverse etiology and complex pathogenesis of SE, combination drug therapy for SE might be more conducive for the treatment of all patients because the combined use of drugs can produce synergistic effects via different mechanisms. This review summarizes combination drug therapies used for SE in animal experiments and clinical practice, the potential advantages of combination drug therapy and specific combination drug therapies using different antiepileptic drugs. The aim is to help researchers seek better treatments for early termination of SE.

Role of JNK isoforms in the kainic acid experimental model of epilepsy and neurodegeneration

“…The currently used antiepileptic drugs are heterogeneous, since they have different mechanisms of action, even though they are not completely well understood (13)(14)(15)(16). One group interacts mainly through the regulation of sodium channels (blockade).…”

“…One group interacts mainly through the regulation of sodium channels (blockade). This is the case of phenytoin, carbamazepine, oxcarbamazepine, valproate, lamotrigine, topiramate, lacosamide and also zonisamide (13,14). In vitro pharmacological studies evidenced that zonisamide and lacosamide enhance slow inactivation of voltage dependent sodium channels © 1996-2017 and reduce calcium entry through voltage dependent calcium channels, thereby stabilizing hyperexcitable neuronal membranes (14)(15)(16).…”

“…This leads to an increase in the intracellular Cl − influx (ion concentration), which induces hyperpolarization of the membrane and inhibition of action potentials, hence rendering the neuron unresponsive for a period. This group includes benzodiazepines, barbiturates, topiramate, felbamate, tiagabine -a potent and selective GABA reuptake inhibitor in neuronal and glial cells-and gabapentin, which inhibits the release of monoamine neurotransmitters and increases GABA turnover in several brain areas (13)(14)(15). Another group of antiepileptic drugs includes pregabalin, gabapentin, topiramate and lamotrigine, which block high voltage calcium channels.…”

“…It acts primarily as a neuronal potassium channel opener, stabilizing the resting membrane potential and controlling neuronal electrical excitability. Thus, retigabine prevents the onset of discharge of epileptogenic potential action (14,16).…”

“…Temporal lobe epilepsy (TLE) is the most common form of human epilepsy with focal seizures, covering 40% of all cases of this neurological disorder. A common subtype is the mesial temporal lobe epilepsy (MTLE), characterized by the presence of seizures originated in limbic areas of the mesial temporal lobe, particularly in the hippocampus, amygdala, and in the parahippocampal gyrus and its connections (11)(12)(13)(14)(15). This type of epilepsy is associated with an "early first insult", such as febrile seizures, a prolonged focal seizure, infection of the central nervous system (CNS), or head trauma, among others, most often occurring in the first five years of life (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12).…”