The Action of Sodium 4‐hydroxybutyrate on Spinal Reflexes

Abstract

The actions of sodium 4-hydroxybutyrate, y-aminobutyric acid and meprobamate have been studied in unanaesthetized animals, in local anaesthetic tests, on isolated organ preparations, on convulsions induced by picrotoxin and strychnine, and on monosynaptic (patellar) and polysynaptic (plantar) reflexes of the spinal cord. Sodium 4-hydroxybutyrate induced a sleep-like state with three unusual features: the righting reflex was remarkably persistent, respiration was good throughout and recovery was abrupt. y-Aminobutyric acid was inactive and meprobamate caused flaccid paralysis with loss of the righting reflex. None of the agents affected the responses of the rat diaphragm either to direct stimulation of the muscle or to indirect stimulation through the phrenic nerve. Only meprobamate reduced the responses of the guinea-pig isolated ileum preparation, showed local anaesthetic action and had an anticonvulsant action. All three compounds were capable, after intravenous or topical application, of blocking plantar reflexes in doses which did not affect the patellar reflex. The spinal animal responded in the same way, to the same dose of sodium 4-hydroxybutyrate, as the decerebrate preparation. Topical application to the motor cortex had no effect on spinal reflexes. We conclude that sodium 4-hydroxybutyrate acts preferentially on the internuncial neurones in the spinal cord but differs from meprobamate in its other actions. The similarity between the actions of sodium 4-hydroxybutyrate and of y-aminobutyric acid provides further evidence in support of the hypothesis that sodium 4-hydroxybutyrate is involved in the y-aminobutyric acid metabolic pathways.

The Excitation and Depression of Mammalian Cortical Neurones by Amino Acids

“…Indeed the latent period between intravenous administration and the depression produced by y-hydroxybutyrate (Drakontides et al, 1962;Basil et al, 1964) suggests that it has an indirect action, possibly as a result of interfering with the metabolism of GABA. It is pertinent to point out that a related substance, y-butyrolactone, which also has central depressant effects (Giarman & Schmidt, 1963) does not increase the brain level of GABA.…”

“…The failure of -y-hydroxybutyric acid to affect central neurones, both cortical and spinal, suggests that the alterations in behaviour, in the electroencephalogram and in spinal reflexes which are produced by this compound are unlikely to be due to a direct action upon central cells (Laborit et al, 1960(Laborit et al, , 1961Drakontides et al, 1962;Basil et al, 1964). Indeed the latent period between intravenous administration and the depression produced by y-hydroxybutyrate (Drakontides et al, 1962;Basil et al, 1964) suggests that it has an indirect action, possibly as a result of interfering with the metabolism of GABA.…”

“…Although not an amino acid, this compound was of interest because of recent reports which indicate that systemic administration of sodium y-hydroxybutyrate results in the depression of activity in animals and humans (Laborit, Jouany, Gerard & Fabiani, 1960;Laborit, Kind & Regil, 1961;Drakontides, Schneider & Funderburk, 1962) and in a reduction of spinal reflexes (Basil, Blair & Holmes, 1964). This compound was ejected electrophoretically as an anion, and in several tests (currents as high as 100 nA) failed to modify either the spontaneous activity of cortical neurones, or the spikes evoked by an excitant amino acid.…”

The Central Action of Gamma-Butyrolactone and Gamma-Hydroxybutyrate

“…The administration of GHB to rats elevated the brain level of GABA (25). By studying the effect of GHB on, the spinal reflex Basil et al (26) concluded that GHB as well as GABA affected the internuncial neurons in the spinal cord., On the other hand, Giarman et al (27) could not find ;the significant change of the revel of brain GABA in the mouse that re ceived GBL, and .Walkenstein et al . (28) and Roth et 'al.…”

Gamma Hydroxybutyric Acid Clinical Pharmacology and Current Status

“…Other systems: Gamma-OH causes muscular hypotonia by depressing spinal internuncial neurones (Basil et al 1964). There is an increase in the amplitude and frequency of uterine contractions during labour and the uterus becomes more sensitive to oxytocic drugs (Alfonsi & Massi 1964).…”