However, in animal experiments, saclofen is paradoxically observed to have an antiepileptic effect. This is probably because GABAB effect is coupled to excitation in the thalamo-cortical circuits — Kir coupling via Gβγ subunits is so strong that it lowers the threshold for T-type Ca2+ channel opening enough to elicit their opening, and thus an excitation in this circuit.
The paradoxical antiepileptic effect of saclofen in animal experiments can be understood through its interaction with thalamo-cortical circuits. The coupling between GABAB receptors and excitation in these networks, facilitated by Kir channels and Gβγ subunits, reduces the threshold for T-type Ca2+ channel activation.