On the mechanism of carbamazepine-induced antinociception in the formalin test.
In the present study, the effect of lidocaine (a sodium channel blocker) on carbamazepine-induced antinociception, in formalin test was investigated. Intraperitoneal (i.p.) administration of different doses of carbamazepine (3.5, 7, 15, and 30 mg/kg) induced a dose-dependent antinociception in mice, in the first and second phases of the test. Different doses of lidocaine as a sodium channel blocker (5, 10, and 20 mg/kg, i.p.) also induced antinociception in both phases of the formalin test. It is noted that lidocaine could potentiate the response of carbamazepine in the first, but not in the second, phase of the formalin test. Meanwhile i.p. administration of different doses of Prazosin, alpha1 adrenoceptor antagonist (0.125, 0.25, and 0.5 mg/kg), Yohimbine, alpha2 adrenoceptor antagonist (0.25, 0.5, and 1 mg/kg), Bicuculline, GABAA receptor antagonist (1.5 and 3 mg/kg), and CGP 35348, GABAB receptor antagonist (100 and 200 mg/kg) exert dose-dependent antinociceptive effect in both phases of the formalin test. It should be noted that bicuculline 0.75 mg/kg by itself increased pain score in the second phase of the formalin test, indicating that blockade of GABAA receptor subtype may induce chronic pain. None of the aforementioned drugs could alter the antinociceptive response of carbamazepine in the formalin test. It is concluded that sodium channel mechanisms may be involved partly in the antinociceptive induced by carbamazepine.
Sahebgharani
Mousa
M
Department of Pharmacology, School of Medicine Tehran University of Medical Sciences, Tehran, Iran.
Hossein-Abad
Ahmad Abdi
AA
Zarrindast
M R
MR
D000317:Adrenergic alpha-Antagonists / Q000627:therapeutic use; D018712:Analgesics, Non-Narcotic / Q000627:therapeutic use*; D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001640:Bicuculline / Q000627:therapeutic use; D002220:Carbamazepine / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D005557:Formaldehyde; D018756:GABA Antagonists / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D009943:Organophosphorus Compounds / Q000627:therapeutic use; D010146:Pain / Q000139:chemically induced / Q000188:drug therapy*; D010147:Pain Measurement / Q000379:methods; D011224:Prazosin / Q000627:therapeutic use; D015016:Yohimbine / Q000627:therapeutic use
D000317:Adrenergic alpha-Antagonists; D018712:Analgesics, Non-Narcotic; D018756:GABA Antagonists; D009943:Organophosphorus Compounds; D005557:Formaldehyde; D015016:Yohimbine; D002220:Carbamazepine; C066430:CGP 35348; D011224:Prazosin; D001640:Bicuculline