Open study of pranlukast add-on therapy in intractable partial epilepsy

Takahashi, Yukitoshi; Imai, Katsumi; Ikeda, Hitoshi; Kubota, Yuko; Yamazaki, Etsuko; Susa, Fuminobu

doi:10.1016/j.braindev.2012.04.001

Cited by 22 publications

(19 citation statements)

References 27 publications

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“…This is in full agreement with the view that application of a two-drug combination with synergistic effects may be beneficial due to the reduction of adverse effects, maintaining anticonvulsant activity [57]. In fact, a recent clinical study has shown that add-on therapy of AEDs used in the clinics with pranlukast, a CysLT 1 receptor antagonist, reduces seizure frequency in patients with intractable partial epilepsy [58]. According to this view, AED polytherapy based on mechanisms of action may enhance effectiveness [57].…”

Section: Discussionsupporting

confidence: 63%

Montelukast potentiates the anticonvulsant effect of phenobarbital in mice: An isobolographic analysis

Fleck

Marafiga

Jesse

et al. 2015

Pharmacological Research

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Section: Discussionsupporting

confidence: 63%

Montelukast potentiates the anticonvulsant effect of phenobarbital in mice: An isobolographic analysis

Fleck

Marafiga

Jesse

et al. 2015

Pharmacological Research

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“…It is important to note several other reports show AEDs inhibit MMP-9 production and protect BBB function in epileptic patients and cerebral ischemic rats [59,60]. It has been proposed that MMP-9 is involved in aberrant synaptic formation in hippocampi of patients with temporal lobe epilepsy [39].…”

Section: Discussionmentioning

confidence: 99%

Disruption of the blood–brain barrier after generalized tonic-clonic seizures correlates with cerebrospinal fluid MMP-9 levels

Wang

Zhang

et al. 2013

J Neuroinflammation

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BackgroundIncreasing evidence suggests seizures cause blood–brain barrier (BBB) dysfunction including decreased seizure threshold and higher onset potential of future seizures. However, the mechanisms underlying BBB damage in seizures remains poorly understood. Evidence in human and animal models shows BBB disruption is associated with activation of matrix metalloproteinase-9 (MMP-9) after cerebral ischemia and inflammation. The objective of this study was to determine whether MMP-9 concentrations in cerebral spinal fluid (CSF) are associated with BBB disruption in patients after epileptic seizures.MethodsThirty-one patients with generalized tonic-clonic (GTC) seizures were included in the study: 20 had recurrent GTC seizures (RS), and 11 had a single GTC seizure (SS) episode. Twenty-five adult non-seizure patients were used as controls. CSF samples were collected by lumbar puncture within 24 h after seizure cessation (range: 3–15 h, mean 6.2 h). CSF MMP-9 levels were determined by an enzyme-linked immunosorbent assay (ELISA). MMP enzyme activity was measured by gelatin zymography. The CSF/serum albumin ratio (albumin quotient, QAlb) was used as a measure of blood–brain barrier permeability.ResultsWe found significantly higher CSF MMP-9 concentrations in seizure patients compared with controls (P < 0.001). CSF MMP-9 levels and QAlb values were higher in RS patients compared with SS and controls. Moreover, CSF MMP-9 concentration showed strong correlation between QAlb values (r = 0.76, P < 0.0001) and between CSF leukocyte counts (r = 0.77, P < 0.0001) in patients after seizures. Gelatin zymography showed MMP-9 proteolytic activity only in GTC seizure patients.ConclusionsOur results suggest MMP-9 plays a role in BBB dysfunction, characterized by invasion of leukocytes into the CSF during seizures.

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“…In addition to the drugs discussed above, many others may have antiepileptic effects, including aspirin, pranlukast, and low-dose fish oil [119,120]. However, additional animal experiments and clinical trials are needed to provide further evidence.…”

Section: Adenosinementioning

confidence: 93%

Exploring novel AEDs from drugs used for treatment of non-epileptic disorders

Zheng

Wang

2016

Expert Review of Neurotherapeutics

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Epilepsy is a chronic neurological disease. Although many anti-epileptic drugs (AEDs) have been developed for clinical use, they have no effect on 20-30% of patients and do not generally prevent epileptogenesis. Because of the long development cycle for new AEDs and the high cost, increasing efforts are being made to find anti-epileptic effects among drugs that are already listed for the treatment of other diseases and repurpose them as potential anti-epileptic treatments. Here, we review the progress that has been made in this field as a result of animal and clinical trials of drugs such as rapamycin, everolimus, losartan, celecoxib, bumetanide and other non-epileptic drugs. These drugs can prevent the epileptogenesis, reduce the epileptic pathological changes, and even be used to treat intractable epilepsy. Their mechanisms of action are completely different from those of existing AEDs, prompting researchers to change their perspectives in the search for new AEDs. ARTICLE HISTORY

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Open study of pranlukast add-on therapy in intractable partial epilepsy

Cited by 22 publications

References 27 publications

Montelukast potentiates the anticonvulsant effect of phenobarbital in mice: An isobolographic analysis

Montelukast potentiates the anticonvulsant effect of phenobarbital in mice: An isobolographic analysis

Disruption of the blood–brain barrier after generalized tonic-clonic seizures correlates with cerebrospinal fluid MMP-9 levels

Exploring novel AEDs from drugs used for treatment of non-epileptic disorders

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