Suppressive effects of oxcarbazepine on tooth pulp-evoked potentials recorded at the trigeminal spinal tract nucleus in cats. 2001

S Kiguchi, and K Ichikawa, and M Kojima
Pharmacology Laboratory, Kissei Pharmaceutical Co. Ltd, Minamiazumi, Nagano, Japan. sumiyoshi_kiguchi@pharm.kissei.co.jp

1. The purpose of the present study was to evaluate the antinociceptive effect of oxcarbazepine, a keto derivitive of carbamazepine (an anticonvulsant), in an animal model. To evoke a nociceptive response, we electrically stimulated the maxillary canine tooth pulp (MCTP) in anaesthetized (allobarbital-urethane), spontaneously breathing cats. 2. The evoked potentials were recorded from the superficial layers of the caudal part of the trigeminal spinal tract nucleus (5ST). We examined a slow component with a large amplitude (the P3 component) in evoked compound potentials; its mean conduction velocity was 1.7 m/s, suggesting a response mediated by C-fibres. 3. To confirm that the P3 component was related to pain sensation, we used morphine, a most efficacious antinociceptive agent, in the present study. The P3 component was significantly suppressed by intravenous administration of morphine (3 mg/kg) and was also suppressed by microinjection of morphine (2 microg) into the recording site of the 5ST. These results suggest that the P3 component is involved in the transmission of nociceptive information. 4. We compared the effect of oxcarbazepine with mexiletine; both are known to block neuronal Na+ channels. Intravenous administration of mexiletine suppressed the P3 component at a dose of 5 mg/kg. Microinjection of mexiletine (10 microg) into the recording site of the 5ST tended to suppress the P3 component, but this effect was not significant. 5. Intravenous administration of oxcarbazepine (1-10 mg/kg) caused a dose-dependent inhibition of the P3 component, which was significantly suppressed at 10 mg/kg oxcarbazepine. Intravenous administration of 10,11-dihydro-10-hydroxy-5H-dibenz[b,f]azepine-5-carboxamide (MHD), a metabolite of oxcarbazepine, at doses of 3-30 mg/kg caused a dose-dependent inhibition of the P3 component. Oxcarbazepine was not available for the microinjection study because it is not water soluble. We used MHD for the microinjection study instead of oxcarbazepine, because MHD can be dissolved in water up to 3 mg/mL. Microinjections of MHD (6 microg) into the recording site of the 5ST suppressed the P3 component. These results indicate that oxcarbazepine has an antinociceptive action.

UI MeSH Term Description Entries
D008297 Male Males
D008801 Mexiletine Antiarrhythmic agent pharmacologically similar to LIDOCAINE. It may have some anticonvulsant properties. KO-1173,KO1173,KOE-1173,Mexiletene,Mexiletine Hydrochloride,Mexitil,Mexitil PL,Mexityl,Novo-Mexiletine,KO 1173,KOE 1173,KOE1173,Novo Mexiletine
D008845 Microinjections The injection of very small amounts of fluid, often with the aid of a microscope and microsyringes. Microinjection
D009020 Morphine The principal alkaloid in opium and the prototype opiate analgesic and narcotic. Morphine has widespread effects in the central nervous system and on smooth muscle. Morphine Sulfate,Duramorph,MS Contin,Morphia,Morphine Chloride,Morphine Sulfate (2:1), Anhydrous,Morphine Sulfate (2:1), Pentahydrate,Oramorph SR,SDZ 202-250,SDZ202-250,Chloride, Morphine,Contin, MS,SDZ 202 250,SDZ 202250,SDZ202 250,SDZ202250,Sulfate, Morphine
D009435 Synaptic Transmission The communication from a NEURON to a target (neuron, muscle, or secretory cell) across a SYNAPSE. In chemical synaptic transmission, the presynaptic neuron releases a NEUROTRANSMITTER that diffuses across the synaptic cleft and binds to specific synaptic receptors, activating them. The activated receptors modulate specific ion channels and/or second-messenger systems in the postsynaptic cell. In electrical synaptic transmission, electrical signals are communicated as an ionic current flow across ELECTRICAL SYNAPSES. Neural Transmission,Neurotransmission,Transmission, Neural,Transmission, Synaptic
D011092 Polyethylene Glycols Polymers of ETHYLENE OXIDE and water, and their ethers. They vary in consistency from liquid to solid depending on the molecular weight indicated by a number following the name. They are used as SURFACTANTS, dispersing agents, solvents, ointment and suppository bases, vehicles, and tablet excipients. Some specific groups are NONOXYNOLS, OCTOXYNOLS, and POLOXAMERS. Macrogols,Polyoxyethylenes,Carbowax,Macrogol,Polyethylene Glycol,Polyethylene Oxide,Polyethyleneoxide,Polyglycol,Glycol, Polyethylene,Glycols, Polyethylene,Oxide, Polyethylene,Oxides, Polyethylene,Polyethylene Oxides,Polyethyleneoxides,Polyglycols,Polyoxyethylene
D002220 Carbamazepine A dibenzazepine that acts as a sodium channel blocker. It is used as an anticonvulsant for the treatment of grand mal and psychomotor or focal SEIZURES. It may also be used in the management of BIPOLAR DISORDER, and has analgesic properties. Amizepine,Carbamazepine Acetate,Carbamazepine Anhydrous,Carbamazepine Dihydrate,Carbamazepine Hydrochloride,Carbamazepine L-Tartrate (4:1),Carbamazepine Phosphate,Carbamazepine Sulfate (2:1),Carbazepin,Epitol,Finlepsin,Neurotol,Tegretol
D002415 Cats The domestic cat, Felis catus, of the carnivore family FELIDAE, comprising over 30 different breeds. The domestic cat is descended primarily from the wild cat of Africa and extreme southwestern Asia. Though probably present in towns in Palestine as long ago as 7000 years, actual domestication occurred in Egypt about 4000 years ago. (From Walker's Mammals of the World, 6th ed, p801) Felis catus,Felis domesticus,Domestic Cats,Felis domestica,Felis sylvestris catus,Cat,Cat, Domestic,Cats, Domestic,Domestic Cat
D003782 Dental Pulp A richly vascularized and innervated connective tissue of mesodermal origin, contained in the central cavity of a tooth and delimited by the dentin, and having formative, nutritive, sensory, and protective functions. (Jablonski, Dictionary of Dentistry, 1992) Dental Pulps,Pulp, Dental,Pulps, Dental
D003984 Dibenzazepines Compounds with two BENZENE rings fused to AZEPINES.

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