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  • Title: GABAergic activity of quisqualamine and homoquisqualamine in hemisected spinal cord in vitro preparation.
    Author: Herrero JF.
    Journal: Rev Esp Fisiol; 1994 Mar; 50(1):11-7. PubMed ID: 7527570.
    Abstract:
    alpha-Decarboxylation of excitatory amino acids can produce derivatives with depressant actions on the central nervous system. Examples are aspartate-B-alanine and glutamate-GABA. Quisqualate derivatives by alpha-decarboxylation, Quisqualamine (QUAM) and Homoquisqualamine (HOMOQUAM) (with an extra methylene group in the molecular chain), were studied in isolated spinal cord in vitro preparation. Dose-dependent depolarizations and inhibition of spontaneous ventral root potentials (sVRP) were induced by QUAM and HOMOQUAM in unblocked, Mg2+ free, hemisected cord. Ventral root evoked potentials by electrical stimulation of dorsal root (2ms, 30V, pulse/30 sec) (DR-VRP) remained unchanged. In Tetrodotoxin (TTX) medium, HOMOQUAM showed a twofold increment of relative potency respect to QUAM depolarizations. Actions evoked by QUAM and HOMOQUAM were not affected by the addition of N-Methyl-D-Aspartate (NMDA) receptor blockers Mg2+ and DL-AP5; non-NMDA antagonist CNQX and GABA B receptor antagonist 2-hydroxysaclofen. In presence of GABA A receptor blockers Bicuculline MeCl or Picrotoxin, the actions evoked by QUAM and HOMOQUAM were blocked. The results obtained show that GABA A receptor seemed to mediate QUAM and HOMOQUAM activity in spinal cord in vitro preparation. The addition of a methylene group in the molecular chain increased the potency twice although the kinetic of the drug did not appeared to have changed. The development of new compounds with depressant activity in the central nervous system may be useful in assessing the physiological and therapeutic significance of central GABA receptors, especially if the blockade of spontaneous activity is not followed by an alteration of the neuronal integration and synaptic transmission reflected in the DR-VRP.
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