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Synergism between metformin and analgesics/vitamin B12 in a model of painful diabetic neuropathy.
Pecikoza, Uros; Tomic, Maja; Nastic, Katarina; Micov, Ana; Stepanovic-Petrovic, Radica.
Afiliación
  • Pecikoza U; Department of Pharmacology, University of Belgrade - Faculty of Pharmacy, Vojvode Stepe 450, P.O. Box 146, 11221 Belgrade, Serbia. Electronic address: upecikoza@pharmacy.bg.ac.rs.
  • Tomic M; Department of Pharmacology, University of Belgrade - Faculty of Pharmacy, Vojvode Stepe 450, P.O. Box 146, 11221 Belgrade, Serbia. Electronic address: majat@pharmacy.bg.ac.rs.
  • Nastic K; Department of Pharmacology, University of Belgrade - Faculty of Pharmacy, Vojvode Stepe 450, P.O. Box 146, 11221 Belgrade, Serbia. Electronic address: knastic@pharmacy.bg.ac.rs.
  • Micov A; Department of Pharmacology, University of Belgrade - Faculty of Pharmacy, Vojvode Stepe 450, P.O. Box 146, 11221 Belgrade, Serbia. Electronic address: anamicov@pharmacy.bg.ac.rs.
  • Stepanovic-Petrovic R; Department of Pharmacology, University of Belgrade - Faculty of Pharmacy, Vojvode Stepe 450, P.O. Box 146, 11221 Belgrade, Serbia. Electronic address: radica@pharmacy.bg.ac.rs.
Biomed Pharmacother ; 153: 113441, 2022 Sep.
Article en En | MEDLINE | ID: mdl-36076556
Metformin (a widely used antidiabetic drug) has demonstrated efficacy in models of painful diabetic neuropathy (PDN), as well as certain clinical efficacy in relieving/preventing PDN. This study aimed to determine the type of interaction between metformin and duloxetine/oxycodone/eslicarbazepine acetate [ESL]/vitamin B12 in relieving diabetic pain hypersensitivity. Antihyperalgesic efficacy was determined using a Von Frey apparatus in mice with streptozotocin-induced PDN. We examined metformin's efficacy following oral (acute and prolonged 7-day treatment) and local (spinal and peripheral) application. The examined analgesics were administered in a single oral dose, whereas vitamin B12 was intraperitoneally administered for 7 days. In combination experiments, metformin (prolonged treatment) and analgesics/vitamin B12 were co-administered in fixed-dose fractions of their ED50 values and the type of interaction was determined using isobolographic analysis. Metformin produced dose-dependent antihyperalgesic effects in diabetic mice after oral (acute and prolonged 7-day treatment) and local spinal/peripheral application. Two-drug metformin combinations with analgesics/vitamin B12 also dose-dependently reduced mechanical hyperalgesia. The isobolographic analysis revealed that metformin synergises with analgesics/vitamin B12, with a 6-7 fold dose reduction of both drugs in the examined combinations. In conclusion, metformin reduces hyperalgesia in diabetic animals, most likely by acting at the spinal and peripheral level. Additionally, it synergizes with duloxetine/oxycodone/ESL/vitamin B12 in reducing hyperalgesia. Metformin co-treatment may increase analgesic efficacy and enable the use of lower (and potentially safer) analgesic doses for treating PDN. Combined metformin-vitamin B12 use may provide more effective pain relief and mitigate metformin-induced vitamin B12 deficiency.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Diabetes Mellitus Experimental / Neuropatías Diabéticas / Metformina Límite: Animals Idioma: En Revista: Biomed Pharmacother Año: 2022 Tipo del documento: Article Pais de publicación: Francia
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Diabetes Mellitus Experimental / Neuropatías Diabéticas / Metformina Límite: Animals Idioma: En Revista: Biomed Pharmacother Año: 2022 Tipo del documento: Article Pais de publicación: Francia