Publications by authors named "M A Kolcheva"
We aimed to prepare novel dibenzo [a,d][7]annulen derivatives that act on N-methyl-d-aspartate (NMDA) receptors with potential neuroprotective effects. Our approach involved modifying the tropane moiety of MK-801, a potent open-channel blocker known for its psychomimetic side effects, by introducing a seven-membered ring with substituted base moieties specifically to alleviate these undesirable effects. Our in silico analyses showed that these derivatives should have high gastrointestinal absorption and cross the blood-brain barrier (BBB).
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- N-methyl-D-aspartate receptors (NMDARs) are crucial in various CNS disorders, with current treatments like memantine and ketamine having limitations and side effects.
- Researchers aimed to create a new NMDAR open-channel blocker, K2060, which displays unique inhibitory properties and stronger effectiveness than existing drugs at inhibiting specific NMDAR subtypes.
- K2060 showed promising results in a mouse model, reducing excitatory postsynaptic currents significantly and exhibiting a good safety profile, suggesting its potential as a treatment for NMDAR-related CNS disorders.
Article Synopsis
- Tacrine (THA) has been phased out due to safety concerns but is still used as a framework in drug development for its effectiveness against multiple targets, although its potential for liver toxicity is a major concern.
- Researchers developed 30 new derivatives focusing on minimizing hepatotoxicity while maintaining anticholinesterase properties and targeting specific NMDA receptor subtypes, leading to the identification of two promising candidates, I-52 and II-52.
- Compound I-52 was highlighted as a lead candidate, demonstrating minimal toxicity, favorable neuroprotective effects in behavioral tests, and lower hepatotoxicity compared to traditional THA-based drugs.
Alzheimer's disease (AD) is a complex disease with an unknown etiology. Available treatments, limited to cholinesterase inhibitors and -methyl-d-aspartate receptor (NMDAR) antagonists, provide symptomatic relief only. As single-target therapies have not proven effective, rational specific-targeted combination into a single molecule represents a more promising approach for treating AD, and is expected to yield greater benefits in alleviating symptoms and slowing disease progression.
View Article and Find Full Text PDFNMDA receptors (NMDARs) are ionotropic glutamate receptors that play a key role in excitatory neurotransmission. The number and subtype of surface NMDARs are regulated at several levels, including their externalization, internalization, and lateral diffusion between the synaptic and extrasynaptic regions. Here, we used novel anti-GFP (green fluorescent protein) nanobodies conjugated to either the smallest commercially available quantum dot 525 (QD525) or the several nanometer larger (and thus brighter) QD605 (referred to as nanoGFP-QD525 and nanoGFP-QD605, respectively).
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