Drug-Nutraceutical Co-Crystal and Salts for Making New and Improved Bi-Functional Analgesics
| Autor: | Robin S. Stein, Tomislav Friščić, Dayaker Gandrath, Cristina Mottillo, Oli Abate Fulas, Hatem M. Titi, André Laferrière, Ghada Ayoub, Terence J. Coderre |
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| Rok vydání: | 2020 |
| Předmět: |
Drug
vasodilators media_common.quotation_subject Analgesic lcsh:RS1-441 Pharmaceutical Science CRPS Pharmacology 010402 general chemistry 01 natural sciences co-crystal Article Pentoxifylline lcsh:Pharmacy and materia medica medicine media_common neuropathic pain 010405 organic chemistry business.industry Linsidomine Chronic pain medicine.disease 0104 chemical sciences Clonidine Complex regional pain syndrome antioxidants Neuropathic pain mechanochemistry business topical analgesics medicine.drug |
| Zdroj: | Pharmaceutics Pharmaceutics, Vol 12, Iss 1144, p 1144 (2020) Volume 12 Issue 12 |
| ISSN: | 1999-4923 |
| Popis: | The discovery and development of effective analgesics is greatly lagging behind the steadily rising prevalence of chronic pain. Currently prescribed analgesics for chronic pain are lacking in efficacy mainly due to their narrowly-targeted mechanism of action. Driving neuronal hyperexcitability that underlies symptoms of chronic pain are multiple non-neuronal processes, among which are tissue hypoxia and oxidative stress. Here we demonstrate the design, synthesis, and activity of new multi-component bi-functional analgesic crystalline solids, co-crystals, and salts, based on pairing of vasodilatory anti-hypoxic drugs pentoxifylline, clonidine and linsidomine with antioxidant nutraceuticals protocatechuic acid, &alpha lipoic acid, and caffeic acid. After validation, chemical and structural characterization of these novel salts and co-crystals, topical formulations of the products were tested in a rat model of complex regional pain syndrome. Analgesic effects achieved with the salts and co-crystal exceeded the efficacy and/or potency of constituent compounds indicating that more effective, advanced analgesics can readily be developed by careful pairing of compounds that simultaneously target multiple neural and non-neural processes driving chronic pain. |
| Databáze: | OpenAIRE |
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