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Cerebroprotective Effect of Lamotrigine After Focal Ischemia in Rats

Cerebroprotective Effect of Lamotrigine After Focal Ischemia in Rats

S E Smith, B S Meldrum

Stroke. 1995 Jan;26(1):117-21; discussion 121-2.

PMID: 7839380

Abstract:

Background and purpose:
Glutamate receptor antagonists are protective in animal models of focal cerebral ischemia. Lamotrigine (3,5-diamino-6-[2,3-dichlorophenyl]-1,2,4-triazine) is an anticonvulsant drug that blocks voltage-gated sodium channels and inhibits the ischemia-induced release of glutamate. We describe the cerebroprotective effect of lamotrigine (as the isethionate salt) after middle cerebral artery occlusion in rats.
Methods:
Neurological deficit and infarct volume (visualized by the lack of reduction of 2,3,5-triphenyltetrazolium chloride) 24 hours after permanent left middle cerebral artery occlusion were studied in Fischer rats (n = 8 per group per dose).
Results:
Lamotrigine at 20 mg/kg i.v. over 10 minutes administered immediately after middle cerebral artery occlusion reduced total infarct volume by 31% and cortical infarct volume by 52%. Lamotrigine at 8 mg/kg i.v. over 10 minutes reduced cortical infarct volume by 38%. Lamotrigine at 50 mg/kg i.v. for 10 minutes was not cerebroprotective and induced a decrease of 29 +/- 15 mm Hg in mean arterial blood pressure (P < .05, n = 8). The optimum dose of lamotrigine (20 mg/kg i.v. over 10 minutes) when administered with a 1-hour delay after middle cerebral artery occlusion reduced cortical infarct volume by 41%. Lamotrigine (20 mg/kg i.v. over 10 minutes) with a 2-hour delay after middle cerebral artery occlusion was ineffective. Neurological deficits after 24 hours were improved after immediate treatment with lamotrigine at 20 mg/kg i.v. over 10 minutes.
Conclusions:
The cerebroprotective effect of lamotrigine in rats is limited to a narrow dose range between 8 and 20 mg/kg. Lamotrigine or analogous compounds may be useful when given shortly after the onset of stroke.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP113170868	Lamotrigine isethionate		113170-86-8	Price

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