Journal of pharmacological sciences
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Lamotrigine (LTG) is an anticonvulsant drug used in the treatment of epilepsy and bipolar disorder and it has been known that LTG targets voltage-dependent sodium channels (VGSCs). In this study, we investigated the effect of LTG on the Nav1.4 Na(+) current using HEK293 cells expressing mouse Nav1.4 VGSCs. ⋯ Moreover, 100 μM LTG decreased Nav1.4 Na(+) current around 40% and shifted the V1/2 of the inactivation curve to the hyperpolarization side by 20.96 mV. These findings suggest that LTG inhibits Nav1.4 Na(+) current and modifies the kinetics of the inactivated state.
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Oxaliplatin is a key drug in the treatment of colorectal cancer, but it causes acute and chronic neuropathies in patients. Amitriptyline has widely been used in patients with painful neuropathy. ⋯ Repeated administration of amitriptyline (5 and 10 mg/kg, p.o., once a day) reduced the oxaliplatin-induced mechanical allodynia but not cold hyperalgesia and reversed the oxaliplatin-induced increase in the expression of NR2B protein and mRNA in rat spinal cord. These results suggest that amitriptyline is useful for the treatment of oxaliplatin-induced neuropathy clinically.
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Botulinum toxin type A is a unique candidate for inhibition of pain transmission. In the present study we attempted to see the beneficial actions of A2 neurotoxin (NTX), an active subunit of botulinum toxin type A. ⋯ Spinal application of A2 NTX also showed a potent suppression of thermal hyperalgesia and mechanical allodynia in the spinal cord injury-induced neuropathic pain model. A2 NTX seems to be a long-lasting treatment for diabetic and spinal cord injury-induced neuropathic pain.
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Alzheimer's disease (AD) is a neurodegenerative disease of the brain associated with irreversible cognitive decline, memory impairment, and behavioral changes. Postmortem brains of AD patients reveal neuropathologic features, in particular the presence of senile plaques (SPs) and neurofibrillary tangles (NFTs), which contain β-amyloid peptides and highly phosphorylated tau proteins. Currently, AD can only be definitively confirmed by postmortem histopathologic examination of SPs and NFTs in the brain. ⋯ Several of the PET probes have been shown in clinical trials to be useful for the imaging of β-amyloid plaques in living brain tissue. More recently, the development of PET/SPECT probes for in vivo imaging of NFTs is an active area of study in the field of molecular imaging because the appearance of NFT pathology correlates well with clinical severity of dementia. We will review current research on the development of PET/SPECT imaging probes for in vivo detection of SPs and NFTs and their application to diagnosis and therapy of AD.
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Neurosteroids are known as allosteric modulators of the ligand-gated ion channel superfamily. Voltage-gated sodium channels (Na(v)) play an important role in mediating excitotoxic damages. ⋯ The suppression of I(Na) by pregnenolone sulphate was due to increased inactivation with little change in activation. These findings suggest that pregnenolone sulphate, a metabolite of pregnenolone, suppresses the function of Na(v) via increased inactivation, which may contribute to the neuroprotection.