Statins – Are they anticonvulsant?

Abstract

Statins are the most popular and effective lipid-lowering medications beneficial in hypercholesterolemias and prevention of cardiovascular diseases. Growing evidence supports theory that statins exhibit neuroprotective action in acute stroke, Alzheimer's disease, Parkinson's disease, multiple sclerosis or epilepsy. Hereby, we present available experimental data regarding action of this group of drugs on seizure activity and neuronal cell death. The most commonly examined statins, such as atorvastatin and simvastatin, display anticonvulsant action with only inconsiderable exceptions. However, the mechanism of this effect remains unexplained. Simvastatin, as a lipophilic statin, which can pass blood-brain barrier easily, was recommended as the best candidate for an anticonvulsant agent. Nevertheless, it is still indistinct, whether the protective activity of statins depends on cholesterol lowering properties or its pleiotropic characteristics. One of the most interesting of 3-hydroxy-3-methylglutaryl-coenzyme A inhibitor's actions involves influence on nitric oxide metabolism.

HMG-CoA reductase inhibitor rosuvastatin improves abnormal brain electrical activity via mechanisms involving eNOS

“…In a clinical study, it has been reported that HMG-CoA reductase inhibitor treatment improves cerebral vasomotor reactivity in patients with cerebral small-vessel disease. Furthermore, the effects of statins on the activation of eNOS have been also revealed (Laufs et al, 2002;Kosmidou et al, 2007;Savoia et al, 2011;Zhou et al, 2013;Banach et al, 2014). It has been also shown that the inhibition of NO by using L-NAME reverses the anticonvulsant effect of atorvastatin after penthylenetetrazol-induced seizure Moazzami et al, 2013).…”

“…And only simvastatin enhanced episodic-like memory (Ramirez et al, 2011). According to recent studies, lipophilic simvastatin was recommended as the best candidate as an anticonvulsant agent (Banach et al, 2014). The authors have discussed and concluded that the most probable explanation of the observed anticonvulsant properties of statins is their influence on neurosteroid or NO synthesis in the brain.…”

“…The authors have discussed and concluded that the most probable explanation of the observed anticonvulsant properties of statins is their influence on neurosteroid or NO synthesis in the brain. However, rosuvastatin was not included in this comparison analysis due to the absence of related studies in the literature (Banach et al, 2014). Furthermore, Etminan and colleagues (2010) investigated the beneficial effects of HMG-CoA reductase inhibitors in patients with epilepsy in a clinical study, in which 217 epilepsy patients and 2170 healthy controls were analyzed, and they concluded that the use of HMG-CoA reductase inhibitors decreased the hospitalization risk for epilepsy.…”

“…In fact, action mechanisms of statins are complex and are not only restricted with their effect on blood-lipid level or vascular effect through eNOS solely (Kilic et al, 2005a,b;Banach et al, 2014). Although L-NAME-treatment reversed anticonvulsant effect of rosuvastatin, proapoptotic p53 and caspase-3 expressions were remained reduced in L-NAMEL-NAME/rosuvastatin-treated animals.…”

“…In fact, action mechanisms of statins are complex and not restricted to their effect on hypercholesterolemia solely. Recent studies revealed that statins influence nitric oxide (NO) production in the brain through alleviating iNOS, and enhancing endothelial nitric oxide synthase (eNOS) activity (Banach et al, 2014). Furthermore, the inhibition of NO reversed anti-epileptic activity of atorvastatin Shafaroodi et al, 2012;Moazzami et al, 2013).…”