Neurosteroids in Epilepsy
Neurosteroids in Neuropathic Pain Treatment
Selective Carbonic anhydrase IX inhibitors
Novel anti-inflammatory compounds
selective 17βHSD1 inhibitors
Wild bee venom peptides
Searching for novel drugs potentially useful for therapy of CNS damage belongs to the most investigated topics in contemporary pharmacology and neuroscience. The proposed project is based on the study of biological properties of newly developed 3αC substituted derivatives of pregnanolone and the evaluation of their pharmacotherapeutic potential.
The current medical treatment of the Neuropathic Pain relies on the ion channel blockers (Gabapentin, Pregabalin) or the serotonin up-take blockers (Duloxetine) or the NMDA antagonists (Memantine, Dextromethorphan). Since direct antagonists or agonists or channel blockers can also severely influence physiological functions, they do have serious adverse side effects during the treatment. Our approach is focused on the allosteric modulation of the neuro-receptors which is milder and just changes the sensitivity of the neuro-receptors to endogenous neurotransmitters or agonists.
The new proprietary steroids have proven their efficacy in increasing the reaction threshold to mechanical and thermal stimuli in six different animal models in the rat. They act as positive allosteric modulators of opioid and muscarinic receptors with various activity profiles on individual receptor subtypes.
The development candidate MS-225 shows good efficacy at doses of 1-3 mg/kg in comparison to the positive control by Gabapentin at 50-100 mg/kg. There were no obvious adverse effects observed up to 10 mg/kg. The MS-225 is bioavailable after p.o. administration and penetrates the BBB. However, its pharmacologic properties have to be optimized as the absolute bioavailability ranges at 1%.
The technology is offered for co-development and licensing.
Preclinical stage, in vitro and in vivo testing, lead optimization, toxicology
EP 2,313,424 (04-23-2014), US 8,575,376 (11-05-2013),EP 2,675,821 (07-24-2013), US 2013338383 (08-08-2013), CZ 305733 and PCT/CZ2015/000096
- Institute of Organic Chemistry and Biochemistry AS CR, v.v.i.
- Institute of PhysiologyAS CR, v.v.i.
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