The α and γ subunit-dependent effects of local anesthetics on recombinant GABAA receptors

Sugimoto, Masahiro; Uchida, Ichirō; Fukami, Sakae; Takenoshita, Makoto; Mashimo, Takashi; Yoshiya, Ikuto

doi:10.1016/s0014-2999(00)00463-5

Cited by 47 publications

(20 citation statements)

References 20 publications

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“…It is well-established that a local anesthetic generates seizure discharges emanating mainly from the amygdala and hippocampus in the limbic system (Ingvar and Shapiro, 1981). Lidocaine reduces the Cl − conductance mediated by GABA A postsynaptic receptors (Sugimoto et al, 2000) and decreases the glycinergic tone (Hara et al, 1995). The more accepted mechanism in which lidocaine causes seizures is the reduction of the inhibitory system.…”

Section: Discussionmentioning

confidence: 99%

Hippocampus and amygdala neurotoxicity produced by systemic lidocaine in adult rats

Blas-Valdivia¹,

Cano-Europa²,

Hernández-García³

et al. 2007

Life Sciences

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Section: Discussionmentioning

confidence: 99%

Hippocampus and amygdala neurotoxicity produced by systemic lidocaine in adult rats

Blas-Valdivia¹,

Cano-Europa²,

Hernández-García³

et al. 2007

Life Sciences

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“…The affinity of procaine for other systems include transporters (dopamine (DA): 104 mM, norepinephrine (NE): 217 mM, and serotonin (5HT): 276 mM) and receptors (serotonin (0.1-10 mM, depending on subtype), neuropeptide Y (5 mM), angiotensin (5 mM), endothelin (5 mM), adrenergic (a 2 : 5 mM, b 1 : 100 mM), glycine (1 mM), glutamate (1 mM), and gamma-aminobutyric acid (GABA) (1.5-5.4 mM per subunit); Aoshima et al, 1992;Cunningham and Lakoski, 1988;Fishlock and Parks, 1966;Itoh et al, 1981;Napier, 1992;Ritz et al, 1987;Sharkey et al, 1988;Sugimoto et al, 2000;Sato et al, 2000). It should be noted that for some ligands affinity constants were not determined, but stated doses had no biological effects, such as D 1 and D 2 receptors (Napier, 1992).…”

Section: Introductionmentioning

confidence: 99%

A Potential Cholinergic Mechanism of Procaine's Limbic Activation

Benson

Carson

Kiesewetter

et al. 2004

Neuropsychopharmacol

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The local anesthetic procaine, when administered to humans intravenously (i.v.), yields brief intense emotional and sensory experiences, and concomitant increases in anterior paralimbic cerebral blood flow, as measured by positron emission tomography (PET). Procaine's high muscarinic affinity, together with the distribution of muscarinic receptors that overlaps with brain regions activated by procaine, suggests a muscarinic contribution to procaine's emotional and sensory effects. This study evaluates the effects of procaine on cerebral muscarinic cholinergic receptors in the anesthetized rhesus monkey. Whole brain and regional muscarinic receptor binding was measured before and after procaine administration on the same day in three anesthetized rhesus monkeys with PET and the radiotracer 3-(3-(3[ 18 F]fluoropropylthio)-1,2,5-thiadiazol-4-yl)-1,2,5,6-tetrahydro-1-methylpyridine ([ 18 F]FP-TZTP), a cholinergic ligand that has preferential binding to muscarinic (M 2 ) receptors. On separate days each animal received six different doses of i.v. procaine in a randomized fashion. Procaine blocked up to B90% of [ 18 F]FP-TZTP specific binding globally in a dose-related manner. There were no regional differences in procaine's inhibitory concentration for 50% blockade (IC 50 ) for [ 18 F]FP-TZTP. Tracer delivery, which was highly correlated to cerebral blood flow in previous monkey studies, was significantly increased at all doses of procaine with the greatest increases occurring near procaine's IC 50 for average cortex. Furthermore, anterior limbic regions showed greater increases in tracer delivery than nonlimbic regions. Procaine has high affinity to muscarinic M 2 receptors in vivo in the rhesus monkey. This, as well as a preferential increase of tracer delivery to paralimbic regions, suggests that action at these receptors could contribute to i.v. procaine's emotional and sensory effects in man. These findings are consistent with other evidence of cholinergic modulation of mood and emotion.

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“…In most of these studies, lidocaine inhibited the GABA-induced current [9][10][11]. However, Nordmark et al [12] studied the effect of local anesthetics on the GABA-gated chloride channel in crayfish stretch receptor neurons.…”

Section: Lidocaine and Gaba Signalingmentioning

confidence: 99%

Systemic lidocaine decreases the Bispectral Index in the presence of midazolam, but not its absence

Gottschalk

McKay

Malik

et al. 2012

Journal of Clinical Anesthesia

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The α and γ subunit-dependent effects of local anesthetics on recombinant GABAA receptors

Cited by 47 publications

References 20 publications

Hippocampus and amygdala neurotoxicity produced by systemic lidocaine in adult rats

Hippocampus and amygdala neurotoxicity produced by systemic lidocaine in adult rats

A Potential Cholinergic Mechanism of Procaine's Limbic Activation

Systemic lidocaine decreases the Bispectral Index in the presence of midazolam, but not its absence

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