(-)-Cytisine

(-)-Cytisine is an alkaloid, which occurs naturally in several types of plants as well as in animals feeding on them (see example in reference 1). (-)-Cytisine is a potent and selective agonist of neuronal nAChR². It acts as a partial agonist of β2-containing nAChR³.

EC₅₀s differ for different subunit-composed channels; for recombinant human channels expressed in Xenopus oocytes the following EC₅₀ values were reported: 25 µM, 39 µM, 67 µM, 72 µM, 2.6 µM 0.9 µM and 71 µM for α2/β2, α2/β4, α3/β2, α3/β4, α4/β2, α4/β4 and α7 respectively⁴.

However, in β2-containing channels, the response to acetylcholine (ACh) is largely reduced when applied in combination with (-)-Cytisine⁵. Therefore, when applied in vivo it exerts a compound effect of both activating certain nAchRs and inhibiting the effect of ACh on others. For example, (-)-Cytisine was found to have antidepressant-like effects in several animal models of antidepressant efficacy. This was probably achieved by inhibiting the effect of ACh on α2/β4 channel in the basolateral amygdala⁶.

In another study, the effects of (-)-Cytisine were compared to nicotine. Rats were trained to discriminate nicotine from saline and it was confirmed that (-)-Cytisine had a nicotine-like discriminative effect, but it was much less potent than nicotine itself⁷.