DaveFoster
Member
I posted a previous study showing that lamotrigine lowers blood serotonin, and there's some evidence for having similar effects (and a partial antipsychotic action) in the brain.
Dr. Peat has talked about nitric oxide and its promotion by estrogen, and he's mentioned it as a causal factor in brain aging, which explains lamotrigine's favorable profile in ameliorating Alzheimer's symptoms in rats.
"Depolarization of adult rat forebrain slices with veratrine induced the release of excitatory amino acids (glutamate and aspartate), the synthesis of nitric oxide (NO), and increases in cyclic GMP (cGMP). The NO synthase inhibitors N omega-monomethyl-L-arginine and N omega-nitro-L-arginine methyl ester decreased the release of NO and the levels of cGMP without affecting the release of excitatory amino acids. In contrast, the antiepileptic drug lamotrigine inhibited the release of excitatory amino acids and of NO, and decreased the levels of cGMP without causing a significant direct inhibition of the NO synthase. Furthermore, the synthesis of NO and the increases in cGMP induced by veratrine were partially blocked by the N-methyl-D-aspartate (NMDA) receptor antagonist MK-801 but not by 6-nitro-7-sulphamobenzo (f) quinoxaline-2,3-dione, a non-NMDA receptor antagonist. Neither of these compounds inhibited directly the NO synthase or the release of excitatory amino acids. Thus, these three types of compound act as an inhibitor of voltage-sensitive sodium channels (lamotrigine), as a receptor antagonist (MK-801), or as direct inhibitors of the NO synthase, to block the pathway leading to increased cGMP after veratrine depolarization. It is likely that some of the pharmacological and therapeutic actions shared by these three types of compound are, at least in part, a consequence of inhibition of the synthesis of NO."
Reference: Inhibition by lamotrigine of the generation of nitric oxide in rat forebrain slices. - PubMed - NCBI
Dr. Peat has talked about nitric oxide and its promotion by estrogen, and he's mentioned it as a causal factor in brain aging, which explains lamotrigine's favorable profile in ameliorating Alzheimer's symptoms in rats.
"Depolarization of adult rat forebrain slices with veratrine induced the release of excitatory amino acids (glutamate and aspartate), the synthesis of nitric oxide (NO), and increases in cyclic GMP (cGMP). The NO synthase inhibitors N omega-monomethyl-L-arginine and N omega-nitro-L-arginine methyl ester decreased the release of NO and the levels of cGMP without affecting the release of excitatory amino acids. In contrast, the antiepileptic drug lamotrigine inhibited the release of excitatory amino acids and of NO, and decreased the levels of cGMP without causing a significant direct inhibition of the NO synthase. Furthermore, the synthesis of NO and the increases in cGMP induced by veratrine were partially blocked by the N-methyl-D-aspartate (NMDA) receptor antagonist MK-801 but not by 6-nitro-7-sulphamobenzo (f) quinoxaline-2,3-dione, a non-NMDA receptor antagonist. Neither of these compounds inhibited directly the NO synthase or the release of excitatory amino acids. Thus, these three types of compound act as an inhibitor of voltage-sensitive sodium channels (lamotrigine), as a receptor antagonist (MK-801), or as direct inhibitors of the NO synthase, to block the pathway leading to increased cGMP after veratrine depolarization. It is likely that some of the pharmacological and therapeutic actions shared by these three types of compound are, at least in part, a consequence of inhibition of the synthesis of NO."
Reference: Inhibition by lamotrigine of the generation of nitric oxide in rat forebrain slices. - PubMed - NCBI
