5-Fluorouracil-13C,15N2 is intended for use as an internal standard for the quantification of 5-flurouracil by GC- or LC-MS. 5-Fluorouracil is a pyrimidine analog that irreversibly inhibits thymidylate synthase, blocking the synthesis of thymidine which is required for DNA synthesis. Intracellular metabolites of 5-fluorouracil exert cytotoxic effects by either inhibiting thymidylate synthetase, or through incorporation into RNA and DNA, ultimately initiating apoptosis.
Cefazolin-13C2,15N is intended for use as an internal standard for the quantification of cefazolin by GC- or LC-MS. Cefazolin is a broad-spectrum cephalosporin antibiotic that is active in vitro against various Gram-positive and Gram-negative bacteria (MICs = 0.2-12.5 μg ml). It also inhibits the growth of clinical isolates of S. aureus, E. coli, P. mirabilis, and K. pneumoniae (MICs = 0.1-25 μg ml). In vivo, cefazolin protects against S. aureus, E. coli, and P. mirabilis infection in mice (ED50s = <0.09-1.78, 0.44-3.63, and 2.31-5.2 mg animal, respectively). Formulations containing cefazolin have been used to treat a variety of bacterial infections.
Lamivudine 13C,15N2, an impurity of Lamivudine (BCH-189), functions as an inhibitor of both HIV-1/2 reverse transcriptase and hepatitis B virus reverse transcriptase, classifying it as a nucleoside reverse transcriptase inhibitor (NRTIs).
Zonisamide-13C2,15N is intended for use as an internal standard for the quantification of zonisamide by GC- or LC-MS. Zonisamide is an antiepileptic agent.1 It selectively inhibits the repeated firing of sodium channels (IC50 = 2 μg ml) in mouse embryo spinal cord neurons and inhibits spontaneous channel firing when used at concentrations greater than 10 μg ml.2 In rat cerebral cortex neurons, zonisamide (1-1,000 μM) inhibits T-type calcium channels with a maximum reduction of 60% of the calcium current.3 Zonisamide inhibits H. pylori recombinant carbonic anhydrase (CA) and the human CA isoforms I, II, and V with Ki values of 218, 56, 35, and 21 nM, respectively.4,5 In mice, it has anticonvulsant activity against maximal electroshock seizure (MES) and pentylenetetrazole-induced maximal, but not minimal, seizures (ED50s = 19.6, 9.3, and >500 mg kg, respectively). Zonisamide (40 mg kg, p.o.) prevents MPTP-induced decreases in the levels of dopamine , but not homovanillic acid or dihydroxyphenyl acetic acid , and increases MPTP-induced decreases in the dopamine turnover rate in mouse striatum in a model of Parkinson's disease.6 Formulations containing zonisamide have been used in the treatment of partial seizures in adults with epilepsy. |1. Masuda, Y., Ishizaki, M., and Shimizu, M. Zonisamide: Pharmacology and clinical efficacy in epilepsy. CNS Drug Rev. 4(4), 341-360 (1998).|2. Rock, D.M., Macdonald, R.L., and Taylor, C.P. Blockade of sustained repetitive action potentials in cultured spinal cord neurons by zonisamide (AD 810, CI 912), a novel anticonvulsant. Epilepsy Res. 3(2), 138-143 (1989).|3. Suzuki, S., Kawakami, K., Nishimura, S., et al. Zonisamide blocks T-type calcium channel in cultured neurons of rat cerebral cortex. Epilepsy Res. 12(1), 21-27 (1992).|4. Nishimori, I., Vullo, D., Minakuchi, T., et al. Carbonic anhydrase inhibitors: Cloning and sulfonamide inhibition studies of a carboxyterminal truncated α-carbonic anhydrase from Helicobacter pylori. Bioorg. Med. Chem. Lett. 16(8), 2182-2188 (2006).|5. De Simone, G., Di Fiore, A., Menchise, V., et al. Carbonic anhydrase inhibitors. Zonisamide is an effective inhibitor of the cytosolic isozyme II and mitochondrial isozyme V: Solution and X-ray crystallographic studies. Bioorg. Med. Chem. Lett. 15(9), 2315-2320 (2005).|6. Yabe, H., Choudhury, M.E., Kubo, M., et al. Zonisamide increases dopamine turnover in the striatum of mice and common marmosets treated with MPTP. J. Pharmacol. Sci. 110(1), 64-68 (2009).
L-Tyrosine-13C9,15N is intended for use as an internal standard for the quantification of L-tyrosine by GC- or LC-MS. L-Tyrosine is a non-essential amino acid.1It is produced by hydroxylation of phenylalanine by phenylalanine hydroxylase but can also be obtained from dietary sources or degradation of endogenous proteins, resulting in L-tyrosine release.1,2L-Tyrosine is a precursor in the biosynthesis of catecholamine neurotransmitters, melanins, and thyroid hormones.3Plasma, skeletal muscle, and erythrocyte levels of L-tyrosine are decreased in patients with chronic kidney disease.1 1.Kopple, J.D.Phenylalanine and tyrosine metabolism in chronic kidney failureJ. Nutr.137(6 Suppl 1)1586S-1590S(2007) 2.Webster, D., and Wildgoose, J.Tyrosine supplementation for phenylketonuriaCochrane DB Syst. Rev.2013(6)CD001507(2013) 3.Slominski, A., and Paus, R.Towards defining receptors for L-tyrosine and L-DOPAMol. Cell Endocrinol.99(2)C7-C11(1994)
L-Glutamic acid-15N is the 15N-labeled version of L-Glutamic acid, an excitatory neurotransmitter and an agonist at metabotropic, kainate, NMDA, and AMPA glutamate receptor subtypes. It directly activates the release of dopamine (DA) from dopaminergic terminals.
L-Thyroxine-13C9,15N is intended for use as an internal standard for the quantification of L-thyroxine by GC- or LC-MS. L-Thyroxine is a synthetic form of the thyroid hormone thyroxine. In vivo, L-thyroxine (0.9 and 2.7 μg) inhibits synthesis and release of thyrotropin induced by thyrotropin-releasing hormone from the anterior pituitary in mice. It also reverses decreases in levels of circulating thymic serum factor (FTS) and the number of T rosette-forming cells in an old age-induced mouse model of hypothyroidism. Formulations containing L-thyroxine have been used in the treatment of hypothyroidism.
L-Arginine-15N4 ((S)-(+)-Arginine-15N4) hydrochloride, the 15N-labeled variant of L-Arginine hydrochloride ((S)-(+)-Arginine hydrochloride), serves as the nitrogen donor in the synthesis of nitric oxide. This potent vasodilator is crucial, especially during a sickle cell crisis where its levels are notably diminished.
Zanamivir-13C,15N2is intended for use as an internal standard for the quantification of zanamivir by GC- or LC-MS. Zanamivir is a sialic acid analog that inhibits neuraminidase release of newly replicated influenza virus particles.1It has been shown to selectively inhibit the growth of influenza A and B viruses in plaque reduction assays with IC50values ranging from 5 to 14 nM and to directly inhibit influenza A and B virus neuraminidases with IC50values ranging from 0.6 to 7.9 nMin vitro. Intranasal zanamivir administration at 0.4 mg kg twice daily reduces mortality and viral titers in lung homogenates of mice infected with influenza. 1.Elliott, M.Zanamivir: From drug design to the clinicPhilos. Trans. R. Soc. Lond. B Biol Sci.356(1416)1885-1893(2001)
Guanfacine-13C,15N3is intended for us as an internal standard for the quantification of guanfacine by GC- or LC-MS. Guanfacine is an α2-adrenergic receptor (α2-AR) agonist with Kivalues of 93, 1,380, and 3,890 nM for α2A-, α2B-, and α2C-ARs, respectively, in a radioligand binding assay.1It has EC50values of 52, 288, and 602 nM for α2A-, α2B-, and α2C-ARs, respectively, for stimulated [35S]GTPγS binding. It also binds to imidazoline receptor 1 (Ki= 19 nM in a radioligand binding assay).2Guanfacine (0.3-5 mg kg) binds to adrenergic receptors in the central nervous system and lowers blood pressure in hypertensive rats in a dose-dependent manner.3It also improves spatial working memory deficits induced by hypobaric hypoxia in rats.4Formulations containing guanfacine are used in the treatment of high blood pressure and attention deficit hyperactivity disorder (ADHD). 1.Jasper, J.R., Lesnick, J.D., Chang, L.K., et al.Ligand efficacy and potency at recombinant α2 adrenergic receptors: Agonist-mediated [35S]GTPγS bindingBiochem. Pharmacol.55(7)1035-1043(1998) 2.Nikolic, K., Filipic, S., and Agbaba, D.QSAR study of imidazoline antihypertensive drugsBioorg. Med. Chem.16(15)7134-7140(2008) 3.Scholtysik, G.Pharmacology of guanfacineBr. J. Clin. Pharmacol.10(Suppl 1)21S-24S(1980) 4.Kauser, H., Sahu, S., Kumar, S., et al.Guanfacine is an effective countermeasure for hypobaric hypoxia-induced cognitive declineNeuroscience254110-119(2013)