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Acute effects of vitamin B6 and fixed combinations of vitamin B1, B6, B12 on nociceptive activity evoked in the rat thalamus: Dose-response relationship and combinations with morphine and paracetamol
Authors:I Jurna  K -H Carlsson  W Kömen  D Bonke
Institution:(1) Institut für Pharmakologie und Toxikologie der Universität des Saarlandes, Homburg/Saar;(2) E. Merck Clinical Drug Devel., Darmstadt
Abstract:Summary Nociceptive activity was elicited in neurones of the thalamus by supramaximal electrical stimulation of afferent C fibres in the sural nerve of rats under urethane anesthesia. The fixed combination of vitamin B1, B6, B12 (Neurobion®) as well as of vitamin B6 administered by i.p. injection dose-dependently reduced the evoked nociceptive activity. The ED50 of Neurobion® is 4.6 ml/kg (at 100 min after injection) and that of vitamin B6 is 189mg/kg (at 90 min after injection). The minimum effective doses of Neurobion® and vitamin B6 are 0.5 ml/kg and 40 mg/kg, respectively. When Neurobion® or vitamin B6 were given at their minimum effective doses, and the minimum effective doses of morphine (0.025 mg/kg) or paracetamol (5 mg/kg) were injected i.v. 80 min later, i.e., when the maximum effect of higher doses of Neurobion® or vitamin B6was about to develop, no supraadditive effect developed. It is concluded that the antinociceptive effect caused by a single injection of Neurobion® is largely due to vitamin B6. Vitamin B12 may contribute to this effect, whereas vitamin B1 alone exhibited only a slight effect on nociception. Moreover, it appears that Neurobion® produces its antinociceptive effect after a single injection and after repeated administration during several days by different mechanisms so that the effect of analgesic agents is not enhanced following a single injection of Neurobion® but may be enhanced after repeated administration of the compound.
Keywords:Vitamin B combination  Vitamin B6  Combined administration: Morphine/Paracetamol  Antinociception  Evoked nociceptive activity  Analgesia  Thalamus  Rat  Acute experiment
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