ANTINOCICEPTION INDUCED BY A NOVEL BENZODIAZEPINE RECEPTOR AGONIST AND BRADYKININ RECEPTOR ANTAGONIST IN RODENT ACUTE AND CHRONIC PAIN MODELS
Nikolay Ya. Golovenko, Natali I. Voloshchuk, S. A. Andronati, I. V. Taran, ?. S. Reder, ?. S. Pashynska, V. B. Larionov*
ABSTRACT
The mechanisms and antinociceptive effects of a novel benzodiazepine receptor agonist and bradykinin receptor antagonist, 7- bromo-5-(o-chlorophenyl)-3-propoxy-1,2-dihydro-3H-1,4-benzodiazepin-2-one (propoxazepam) were studied on animal models of acute and chronic pain and compared to the antinociceptive profiles of gabapentin and ketorolac. We also studied the possible role of GABAergic and bradykinin-ergic system on propoxazepam effects. The effects of propoxazepam on pain responses were examined using tail-flick test (TFT) in rats, streptozotocin-induced rat model (SPZ) and sciatic nerve injury (SNI)-induced hyperalgesia in rats. Propoxazepam (3 mg/kg)) produced statistically significant analgesic effect compared to the control and ketorolac values after acute application in TFT and SNI-induced hyperalgesia in rats. Propoxazepam (2 mg/kg) in compare to gabapentin (5 mg/kg) in greater degree after both acute single and chronic administrations produced analgesic action in SPZ-diabetic rats. Propoxazepam administration reduced bradykinin-induced (0.01%) hyperalgesia. At low dose (1 mg/kg) flumazenil diminished propoxazepam antinociceptive effect while at higher dose (10 mg/kg) had nearly no influence, possibly due to GABA-receptor complex stabilization. These results suggest that propoxazepam causes both nociceptive and neuropathic analgesia in rats and GABAA-receptor and bradykinin B-receptor are a key sites of the analgesic action of propoxazepam.
Keywords: Propoxazepam, antinociception, neuropathic pain, streptozotocin-induced diabetes, benzodiazepine receptor agonist, bradykinin antagonist.
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