Concentration-Dependent Blockade of I_Na and I_h by Topiramate in Excitable Cells

Concentration-Dependent Blockade of I_Na and I_h by Topiramate in Excitable Cells

Topiramate (TPM), a sulfamate-substituted monosaccharide, is a broad-spectrum anticonvulsant widely prescribed for epilepsy, migraine prophylaxis, and neuropathic pain. Its therapeutic efficacy stems from multifaceted interactions with ion channels, neurotransmitter receptors, and enzymes; however, the precise mechanisms governing its modulation of plasmalemmal ionic currents—particularly voltage-gated sodium currents (I_Na) and hyperpolarization-activated cation currents (I_h)—remain incompletely characterized. Prior studies have implicated TPM in sodium channel blockade, yet inconsistencies persist regarding concentration-dependent effects, gating kinetics, and interactions with other currents. This study employs patch-clamp techniques in GH₃ rat lactotrophs, an established model for excitable cells, to provide comprehensive evidence of TPM’s “dual block” on I_Na and I_h, elucidating potential contributions to its neuromodulatory profile.

FDA Approves LEQEMBI IQLIK for At-Home Alzheimer’s Maintenance Therapy

FDA Approves LEQEMBI IQLIK for At-Home Alzheimer’s Maintenance Therapy

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by amyloid-beta (Aβ) accumulation, including toxic protofibrils, driving cognitive decline in patients with mild cognitive impairment (MCI) or mild dementia. Maintenance therapy is critical to sustain clinical benefits after initial treatment, yet accessible options are limited. Lecanemab, a monoclonal antibody targeting Aβ aggregates, has shown efficacy in slowing AD progression, but IV administration poses logistical challenges. The objective is to evaluate the efficacy, safety, and usability of LEQEMBI IQLIK (lecanemab-irmb), a subcutaneous autoinjector for weekly maintenance dosing in early AD, following 18 months of IV initiation therapy.

Updated ACP Guidelines on Preventing Episodic Migraines

Updated ACP Guidelines on Preventing Episodic Migraines

The American College of Physicians (ACP) has issued new guidelines to prevent episodic migraines among adults, specifically for primary care physicians who see patients who are not taking preventive migraine drugs previously.

Mirdametinib Gains FDA Nod for NF1-PN

Mirdametinib Gains FDA Nod for NF1-PN

The FDA approved mirdametinib (Gomekli) for adults and children 2 years and older with neurofibromatosis type 1 (NF1) and symptomatic plexiform neurofibromas (PN) that are not resectable surgically.