TABLE 1.
Drug (trade names) | Mechanism of action | Current drug indications |
---|---|---|
Gabapentin (Fanatrex, Gabarone, Gralise, Neurontin) |
Originally thought to be a GABA mimetic, but mechanism of action is now unclear. Possible enhancement of GABA synthesis could explain why ambient GABA levels in the brain are raised1. |
Partial-onset seizures in adults and the elderly2 Alcohol withdrawal as a combination therapy3 Sleep disorders4 |
Vigabatrin (Sabril) |
Irreversible block of GABA transaminase to interfere with GABA cetabolism and, therefore, raise ambient GABA levels. |
Refractory complex partial seizures and infantile spasms5. Not favoured due to visual field loss in some adults and children6. |
Tiagabine (Gabitril) |
Blockade of GABA transporters on nerve terminals (predominantly GAT-1) leads to raised ambient GABA levels. |
Partial seizures Generalized anxiety disorders/panic disorders7 |
Pregabalin (Lyrica) |
Enhances the activity of glutamic acid decarboxylase (GAD) leading to increased GABA synthesis and, therefore, raised ambient GABA levels. |
Partial seizures with or without secondary generalization8 Neuropathic pain in diabetese, post herpetic neuralgia and fibromyalgia8. Generalized anxiety disorder8. |
Gaboxadol | Selective orthosteric agonist at δ-GABAARs leading to specific enhancement of the tonic conductance. |
Sleep enhancer, but withdrawn from Phase III clinical trials due to poor risk-to-benefit ratio9. |
L-655,708 | High-affinity negative allosteric modulator of α5-GABAARs that will reduce tonic conductances. |
Cognitive enhancer but not thought to be suitable for human use due to anxiogenic properties10. |
Ganaxolone | Positive allosteric modulator of most GABAARs with greater potency at δ-GABAARs leading to selective enhancement of the tonic conductance. |
Catemenial epilepsy11 |
Alphaxalone (Althesin, Saffan) |
Positive allosteric modulator of most GABAARs with greater potency at δ-GABAARs leading to selective enhancement of the tonic conductance. |
Anaesthetic12 and sedative in long-term intensive care patients13. Was withdrawn from clinical practice due to complications with the vehicle, Cremophor EL. Re-branded as Saffan and widely used as an anaesthetic in veterinary surgery. |
Propofol (Diprivan) |
Positive allosteric modulator of most GABAARs including α5 and δ-GABAARs leading to enhanced tonic conductance. |
Widely used as an intravenous anaesthetic. |
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Winter L, Nadeson R, Tucker AP, Goodchild CS. (2003) Antinociceptive properties of neurosteroids: a comparison of alphadolone and alphaxalone in potentiation of opioid antinociception, Anesth. Analg. 97 798–805.
Stewart GO, Dobb GJ, Craib IA. (1983) Clinical trial of continuous infusion of alphaxalone/alphadolone in intensive care patients. Anaesth Intensive Care. 11(2):107–12.