1990 Jan 19;68(2):129-35.Jurna I1, Carlsson KH, Kömen W, Bonke D.Author information1Institut für Pharmakologie und Toxikologie der Universität des Saarlandes, Homburg/Saar.AbstractNociceptive 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, and 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 189 mg/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 B6 was 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.PMID: 2157085 [Indexed for MEDLINE] Publication typeComparative StudyMeSH termsAcetaminophen/pharmacology*Afferent Pathways/drug effectsAnimalsDose-Response Relationship, DrugDrug SynergismFemaleMaleMorphine/pharmacology*Neurons/drug effectsNociceptors/drug effects*Pyridoxine/pharmacology*RatsRats, Inbred StrainsSpinal Cord/drug effectsSural Nerve/drug effectsSynaptic Transmission/drug effectsThalamic Nuclei/drug effects*Vitamin B Complex/pharmacology*SubstancesVitamin B ComplexAcetaminophenMorphinePyridoxineOther Literature SourcesCited by Patents in - The LensMedicalB Vitamins - MedlinePlus Health InformationMiscellaneousPYRIDOXINE HYDROCHLORIDE - Hazardous Substances Data BankMORPHINE - Hazardous Substances Data BankACETAMINOPHEN - Hazardous Substances Data Bank
IDPharmacologyInteractionsReferencesTrialsEconomicsPropertiesSpectraTaxonomyTargets (2)Enzymes (1)Transporters (3)CommentsTargets (2)Enzymes (1)Transporters (3)Biointeractions (4)Get DrugBank to go! Sign up to get early access Details1. Thiamin pyrophosphokinase 1KindProteinOrganismHumanPharmacological actionyesActionsligandGeneral Function:Thiamine diphosphokinase activitySpecific Function:Catalyzes the phosphorylation of thiamine to thiamine pyrophosphate. Can also catalyze the phosphorylation of pyrithiamine to pyrithiamine pyrophosphate.Gene Name:TPK1Uniprot ID:Q9H3S4 Molecular Weight:27265.05 DaReferencesPylypchuk SIu, Parkhomenko IuM, Protasova ZS, Vovk AI, Donchenko HV: [Interaction of rat brain thiamine kinase with thiamine and its derivatives]. Ukr Biokhim Zh (1999). Melnick J, Lis E, Park JH, Kinsland C, Mori H, Baba T, Perkins J, Schyns G, Vassieva O, Osterman A, Begley TP: Identification of the two missing bacterial genes involved in thiamine salvage: thiamine pyrophosphokinase and thiamine kinase.
Bellyei S, Szigeti A, Boronkai A, Szabo Z, Bene J, Janaky T, Barna L, Sipos K, Minik O, Kravjak A, Ohmacht R, Melegh B, Zavodszky P, Than GN, Sumegi B, Bohn H, Than NG: Cloning, sequencing, structural and molecular biological characterization of placental protein 20 (PP20)/human thiamin pyrophosphokinase (hTPK). [PubMed:15664409 ] de Jong L, Meng Y, Dent J, Hekimi S: Thiamine pyrophosphate biosynthesis and transport in the nematode Caenorhabditis elegans. Thiamine transporter 1KindProteinOrganismHumanPharmacological actionunknownActionsbinderGeneral Function:Thiamine uptake transmembrane transporter activitySpecific Function:High-affinity transporter for the intake of thiamine.Gene Name:SLC19A2Uniprot ID:O60779 Molecular Weight:55399.49 DaReferencesLiberman MC, Tartaglini E, Fleming JC, Neufeld EJ: Deletion of SLC19A2, the high affinity thiamine transporter, causes selective inner hair cell loss and an auditory neuropathy phenotype. J Assoc Res Otolaryngol. Epub 2006 Apr 27. Diaz GA, Banikazemi M, Oishi K, Desnick RJ, Gelb BD: Mutations in a new gene encoding a thiamine transporter cause thiamine-responsive megaloblastic anaemia syndrome.
Fleming JC, Tartaglini E, Steinkamp MP, Schorderet DF, Cohen N, Neufeld EJ: The gene mutated in thiamine-responsive anaemia with diabetes and deafness (TRMA) encodes a functional thiamine transporter. Labay V, Raz T, Baron D, Mandel H, Williams H, Barrett T, Szargel R, McDonald L, Shalata A, Nosaka K, Gregory S, Cohen N: Mutations in SLC19A2 cause thiamine-responsive megaloblastic anaemia associated with diabetes mellitus and deafness. Cytochrome P450 4B1KindProteinOrganismHumanPharmacological actionunknownActionsinducerGeneral Function:Oxygen bindingSpecific Function:Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics.Gene Name:CYP4B1Uniprot ID:P13584 Molecular Weight:58990.64 DaReferencesLiu S, Stromberg A, Tai HH, Moscow JA: Thiamine transporter gene expression and exogenous thiamine modulate the expression of genes involved in drug and prostaglandin metabolism in breast cancer cells.
Mol Cancer Res. 2004 Aug;2(8):477-87. Solute carrier family 22 member 2KindProteinOrganismHumanPharmacological actionunknownActionsinhibitorGeneral Function:Quaternary ammonium group transmembrane transporter activitySpecific Function:Mediates tubular uptake of organic compounds from circulation. Mediates the influx of agmatine, dopamine, noradrenaline (norepinephrine), serotonin, choline, famotidine, ranitidine, histamin, creatinine, amantadine, memantine, acriflavine, 4-[4-(dimethylamino)-styryl]-N-methylpyridinium ASP, amiloride, metformin, N-1-methylnicotinamide (NMN), tetraethylammonium (TEA), 1-methyl-4-phenylpyridiniu...Gene Name:SLC22A2Uniprot ID:O15244 Molecular Weight:62579.99 DaReferencesUrakami Y, Akazawa M, Saito H, Okuda M, Inui K: cDNA cloning, functional characterization, and tissue distribution of an alternatively spliced variant of organic cation transporter hOCT2 predominantly expressed in the human kidney. J Am Soc Nephrol. Urakami Y, Okuda M, Masuda S, Akazawa M, Saito H, Inui K: Distinct characteristics of organic cation transporters, OCT1 and OCT2, in the basolateral membrane of renal tubules.
Pharm Res. 2001 Nov;18(11):1528-34. Solute carrier family 22 member 1KindProteinOrganismHumanPharmacological actionunknownActionsinhibitorGeneral Function:Secondary active organic cation transmembrane transporter activitySpecific Function:Translocates a broad array of organic cations with various structures and molecular weights including the model compounds 1-methyl-4-phenylpyridinium (MPP), tetraethylammonium (TEA), N-1-methylnicotinamide (NMN), 4-(4-(dimethylamino)styryl)-N-methylpyridinium (ASP), the endogenous compounds choline, guanidine, histamine, epinephrine, adrenaline, noradrenaline and dopamine, and the drugs quinine...Gene Name:SLC22A1Uniprot ID:O15245 Molecular Weight:61153.345 DaReferencesBednarczyk D, Ekins S, Wikel JH, Wright SH: Influence of molecular structure on substrate binding to the human organic cation transporter, hOCT1. Sinclair CJ, Chi KD, Subramanian V, Ward KL, Green RM: Functional expression of a high affinity mammalian hepatic choline/organic cation transporter.
J Lipid Res. 2000 Nov;41(11):1841-8. Green RM, Lo K, Sterritt C, Beier DR: Cloning and functional expression of a mouse liver organic cation transporter. Solute carrier family 22 member 5KindProteinOrganismHumanPharmacological actionunknownActionsinhibitorGeneral Function:Symporter activitySpecific Function:Sodium-ion dependent, high affinity carnitine transporter. Involved in the active cellular uptake of carnitine. Transports one sodium ion with one molecule of carnitine. Also transports organic cations such as tetraethylammonium (TEA) without the involvement of sodium. Also relative uptake activity ratio of carnitine to TEA is 11.3.Gene Name:SLC22A5Uniprot ID:O76082 Molecular Weight:62751.08 DaReferencesOhashi R, Tamai I, Nezu Ji J, Nikaido H, Hashimoto N, Oku A, Sai Y, Shimane M, Tsuji A: Molecular and physiological evidence for multifunctionality of carnitine/organic cation transporter OCTN2. Wu X, Huang W, Prasad PD, Seth P, Rajan DP, Leibach FH, Chen J, Conway SJ, Ganapathy V: Functional characteristics and tissue distribution pattern of organic cation transporter 2 (OCTN2), an organic cation/carnitine transporter.