Convulsant actions of calycanthine

The principal alkaloid of the family Calycanthaceae, calycanthine has long been recognized as a central convulsant. The alkaloid inhibited the potassium-stimulated release of [³H]GABA from slices of rat hippocampus with an ED₅₀ of ∼21 μM. This effect appeared to be moderately selective since calycanthine at 100 μM had only a weak effect on the potassium-stimulated release of [³H]acetylcholine (15%) and no significant effects on the release of [³H]D-aspartate from hippocampal and cerebellar slices or the release of [³H]glycine from spinal cord slices. Calycanthine blocked the L-type calcium currents with an IC₅₀ of ∼42 μM and also weakly inhibited the N-type calcium currents (IC₅₀ > 100 μM) from neuroblastoma X glioma cells, suggesting voltage-dependent calcium channel blockade as a possible mechanism for its inhibition of GABA and ACh release. Calycanthine was also found to directly inhibit GABA-mediated currents (K_B ∼135 μM) from human α₁β₂γ_2L GABA_A receptors expressed in Xenopus laevis oocytes but had no effect at 100 μM on human ρ₁ GABA_c receptors. The results indicated that calycanthine may mediate its convulsant action predominantly by inhibiting the release of the inhibitory neurotransmitter GABA as a result of interactions with L-type Ca²⁺ channels and by inhibiting GABA-mediated chloride currents at GABA_A receptors.