Abstract
The N-methyl-D-aspartate (NMDA) receptor subclass of excitatory amino acid receptors has been implicated in pathological conditions such as epilepsy, ischemia, and hypoglycemia. Antagonists of the NMDA receptor have been shown to block these conditions when induced in experimental animals. One of the most specific and potent NMDA antagonists is 2-amino-7-phosphono-heptanoate (APH), with the majority of the activity residing in the D-isomer. The racemic mixture of APH, injected intraperitoneally into mice at doses of 0.33–1.0 mmol/kg, is effective against either sound or chemically induced seizures [1]. APH has also been shown to protect against ischemia induced by bilateral carotid occlusion [2] and neuronal damage due to hypoglycemia [3]. Although these studies have demonstrated the effectiveness of APH in these pathological conditions, only limited information on the pharmacokinetics of APH is available, and it is not clear whether D,L-APH and D-APH would demonstrate different pharmacokinetic properties in blood and appearance in cerebrospinal fluid. The present study describes an analytical method for the. quantification of APH in plasma and cerebrospinal fluid. Additionally, the pharmacokinetics of D-APH and D,L-APH in the rat are reported.
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© 1988 Kluwer Academic Publishers
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Compton, R.P., Kreiter, P.A., Smith, R.G., Harken, R.D., Monahan, J.B. (1988). Determination of the Pharmacokinetics of 2-Amino-7-Phosphonoheptanoate in Plasma and Cerebrospinal Fluid. In: Ferrendelli, J.A., Collins, R.C., Johnson, E.M. (eds) Neurobiology of Amino Acids, Peptides and Trophic Factors. Topics in the Neurosciences, vol 8. Springer, Boston, MA. https://doi.org/10.1007/978-1-4613-1721-0_16
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DOI: https://doi.org/10.1007/978-1-4613-1721-0_16
Publisher Name: Springer, Boston, MA
Print ISBN: 978-1-4612-8969-2
Online ISBN: 978-1-4613-1721-0
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