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Br J Pharmacol
2003 Mar 01;1385:876-82. doi: 10.1038/sj.bjp.0705107.
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Local anaesthetics have different mechanisms and sites of action at the recombinant N-methyl-D-aspartate (NMDA) receptors.
Sugimoto M
,
Uchida I
,
Mashimo T
.
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(1) Although the principal pharmacological targets of local anaesthetics (LAs) are voltage-gated Na(+) channels, other targets have also been suggested. Here we examined the effects of LAs on the N-methyl-D-aspartate (NMDA) receptor, a receptor involved in the process of nociception. (2) LAs (bupivacaine, lidocaine, procaine, and tetracaine) reversibly and concentration-dependently inhibited recombinant epsilon1/zeta1 and epsilon2/zeta1 NMDA receptors expressed in Xenopus oocytes (IC(50)s for bupivacaine, lidocaine, procaine, and tetracaine were 1032.0, 1174.1, 642.1 and 653.8 micro M at the epsilon1/zeta1 receptor; and 1090.8, 1821.3, 683.0 and 662.5 micro M respectively (at the epsilon2/zeta1 receptor). Bupivacaine and procaine were non-competitive antagonists; bupivacaine possesses non-competitive and competitive actions when interacting with glycine, whereas procaine has only non-competitive action. (3) Mutation of asparagine residue at position 598 (Asp(598)) in the zeta1 subunit, a residue associated with the blockade site for Mg(2+) and ketamine, to glutamine or arginine reduced the sensitivity to procaine but not to bupivacaine. Thus, procaine may interact with sites of action that are closely related to those of Mg(2+) and ketamine blockade. (4) These results suggest that LAs inhibit the NMDA receptor by various mechanisms.
BROMAGE,
Local anesthetic drugs: penetration from the spinal extradural space into the neuraxis.
1963, Pubmed
BROMAGE,
Local anesthetic drugs: penetration from the spinal extradural space into the neuraxis.
1963,
Pubmed
CONVERSE,
The concentration of pontocaine hydrochloride in the cerebrospinal fluid during spinal anesthesia, and the influence of epinephrine in prolonging the sensory anesthetic effect.
1954,
Pubmed
Cohen,
Distribution of local anesthetic agents in the neuraxis of the dog.
1968,
Pubmed
Colquhoun,
Binding, gating, affinity and efficacy: the interpretation of structure-activity relationships for agonists and of the effects of mutating receptors.
1998,
Pubmed
Dingledine,
The glutamate receptor ion channels.
1999,
Pubmed
Fan,
Effect of cocaine on the 5-HT3 receptor-mediated ion current in Xenopus oocytes.
1995,
Pubmed
,
Xenbase
Franks,
How does xenon produce anaesthesia?
1998,
Pubmed
Hara,
Local anesthetics reduce the inhibitory neurotransmitter-induced current in dissociated hippocampal neurons of the rat.
1995,
Pubmed
Jevtović-Todorović,
Nitrous oxide (laughing gas) is an NMDA antagonist, neuroprotectant and neurotoxin.
1998,
Pubmed
Kasaba,
Bupivacaine-induced convulsion is suppressed by MK-801.
1998,
Pubmed
Komai,
Local anesthetic inhibition of voltage-activated potassium currents in rat dorsal root ganglion neurons.
2001,
Pubmed
Liu,
Modulation of NMDA receptor function by ketamine and magnesium: Part I.
2001,
Pubmed
,
Xenbase
Liu,
Effects of bupivacaine and ropivacaine on high-voltage-activated calcium currents of the dorsal horn neurons in newborn rats.
2001,
Pubmed
Lu,
Inhibition of nicotinic cholinoceptor mediated current in vagal motor neurons by local anesthetics.
1996,
Pubmed
Mori,
Identification by mutagenesis of a Mg(2+)-block site of the NMDA receptor channel.
1992,
Pubmed
,
Xenbase
Mori,
Structure and function of the NMDA receptor channel.
1995,
Pubmed
Nishizawa,
The inhibition of the N-methyl-D-aspartate receptor channel by local anesthetics in mouse CA1 pyramidal neurons.
2002,
Pubmed
Post,
A new method for studying the distribution of drugs in spinal cord after intrathecal injection.
1984,
Pubmed
Sugimoto,
The alpha and gamma subunit-dependent effects of local anesthetics on recombinant GABA(A) receptors.
2000,
Pubmed
,
Xenbase
Tölle,
The differential expression of 16 NMDA and non-NMDA receptor subunits in the rat spinal cord and in periaqueductal gray.
1993,
Pubmed
Ushijima,
Cocaine: evidence for NMDA-, beta-carboline- and dopaminergic-mediated seizures in mice.
1998,
Pubmed
Woolf,
Neuronal plasticity: increasing the gain in pain.
2000,
Pubmed
Yamakura,
Different sensitivities of NMDA receptor channel subtypes to non-competitive antagonists.
1993,
Pubmed
,
Xenbase
Yamakura,
Subunit- and site-specific pharmacology of the NMDA receptor channel.
1999,
Pubmed
