Directly acting Gabamimetic drugs
The distinction between directly and indirectly acting gabamimetic is often difficult to establish and certain drugs have the two types of effects.
With GABA-A effects
There are several drugs having GABA-A effects.
Propofol
Propofol is an injectable short-acting general anesthetic largely used for the induction and maintenance of general anesthesia and whose mechanism of action remains unclear. Its sedating effect could be the consequence of direct stimulation of GABA-A receptors, but it could moreover inhibit GABA reuptake by presynaptic terminations. Its use in children under fifteen is contra-indicated.
Inhalational anesthetics
Inhalational halogenated anesthetics such as halothane, isoflurane, enflurane, desflurane, sevoflurane have an asymmetrical carbon in their molecule. The comparison of activity of isomers S and R indicates that active enantiomers induce chloride entry into cells by modulation of GABA-A receptor activity in a manner which remains to be clarified, probably by direct stimulation by acting on a site different from that of propofol. Recent studies suggest that they induce intracellular potassium exit by opening potassium channels of a particular type, with two pores. Administered by inhalation, they are primarily eliminated by pulmonary route but a part is metabolized in the liver with fluoride release.
Among their possible adverse effects, the risk of malignant hyperthermia has been reported.
Halothane |
FLUOTHANE* |
Isoflurane |
FORENE*, FORANE* |
| Enflurane |
ETHRANE* |
| Desflurane |
SUPRANE* |
| Sevoflurane |
SEVORANE*, ULTANE* |
Notice 1:
Progabide is a direct agonist of GABA-A receptors with antiepileptic properties, active in many forms of epilepsy. Because it frequently caused hepatatis, it was used only in epilepsies resistant to other drugs before being withdrawn from the market.
Notice 2:
Piperazine has an antihelminthic activity by stimulation of the GABA-A receptors of intestinal parasites like Ascaris. The receptors of parasites differ however from human receptors, which explains why piperazine has few effects in human beings.
With GABA-B effects: baclofen
The only drug with GABA-B effect is baclofen. Baclofen, is an agonist of GABA-B receptors, it inhibits monosynaptic and polysynaptic reflex transmission in the spinal cord and has a muscular relaxant effect.
Its principal therapeutic uses are spastic contractures of various neurological affections (multiple sclerosis, paraplegia). It could have an interest in treatment of tetanus contractures.
Baclofen frequently elicits drowsiness and following its brutal discontinuation, especially when it is given by intrathecal infusion, psychiatric disorders (confusional states, psychosis), seizures, muscular rigidity.
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