Analgesic and antiallodynic properties of new 3,3-diphenyl-propionamides with anticonvulsant activity
INTRODUCTION: Apart from epilepsy treatment, anticonvulsant drugs are also extensively used as efficacious therapy of diverse non-epileptic conditions, including pain (neuropathic pain, migraine prophylaxis), neuromuscular disorders and psychiatric disorders (anxiety, bipolar affective disorder). Therefore, continued preclinical searching for new anticonvulsant drugs with collateral antinociceptive activity are expected since they lead to further advancements in the treatment of epilepsy, as well as neuropathic pain. AIM(S): The aim of the study was to examine analgesic activity of three new 3,3-diphenyl-propionamides, which demonstrated in the previous research anticonvulsant activity in the MES (the maximal electroshock seizure) and scPTZ (subcutaneous pentylenetetrazole) tests in mice. METHOD(S): The antinociceptive properties were estimated in four models of pain in mice – the hot plate test (acute pain), the formalin test (tonic pain), the oxaliplatin-induced neuropathy (neuropathic pain), and the streptozotocin-induced diabetic neuropathy. RESULTS: In the hot plate test the greatest effect possessed compound JOA 122, which at a dose of 30 mg/kg significantly prolonged the latency time to pain reaction. In the formalin test a significant antinociceptive activity was observed for compounds JOA 122 and JOA 123 in the second (late) phase. In this phase the compound JOA 122 tested at the doses 1, 10, 30 mg/kg reduced duration of licking response. Compound JOA 123 attenuated the nocifensive response in this phase only at the dose 30 mg/kg. In the oxaliplatin-induced neuropathy, as well as streptozotocin-induced neuropathy tested compounds at the dose of 30 mg/kg attenuated tactile allodynia, since they significantly elevated the pain sensitivity threshold in the acute phase. CONCLUSIONS: The results obtained in the current studies proved that in the group of novel 3,3-diphenyl-propionamides new anticonvulsants with collateral analgesic properties can be found. FINANCIAL SUPPORT: Supported by the grant of the Polish National Scientific Centre, Poland (Grant No. DEC-2013/11/B/NZ7/02081).