Rotigotine (Hydrochloride)

Rotigotine Hydrochloride (N-0923 Hydrochloride) is a full agonist of dopamine receptor, a partial agonist of the 5-HT1A receptor, and an antagonist of the α2B-adrenergic receptor, with K_i of 0.71?nM, 4-15?nM, and 83?nM for the dopamine D3 receptor and D2, D5, D4 receptors, and dopamine D1 receptor. IC50 & Target: Ki: 0.71?nM (dopamine D3 receptor), 4-15?nM (dopamine D2, D5, D4 receptors), 83?nM (dopamine D1 receptor)^[1][2], 176 nM (α1A), 273 nM (α1B), 338 nM (α2A), 27 nM (α2B), 30 nM (5-HT1A), 86 nM (5-HT7)^[2] In Vitro: Rotigotine (N-0923) has a 10-fold selectivity for D3 (pK_i 9.2) receptors compared with D2, D4 and D5 (pK_i 8.5-8.0) and a 100-fold selectivity compared with D1 receptors (pK_i 7.2). In functional studies, Rotigotine (N-0923) behaves as full agonist at all dopamine receptors but notably the potency for stimulation of D1 receptors is similar to that for D2 and D3 receptors (pEC₅₀ respectively: 9.0, 9.4-8.6, 9.7)^[1]. Rotigotine (N-0923) (10 μM) decreases the number of THir neurons by 40% in primary mesencephalic cell culture. Rotigotine (0.01 μM) slightly protects dopaminergic neurons against MPP⁺ toxicity, significantly protects dopaminergic neurons against rotenone-induced cell death, and significantly inhibits ROS production by rotenone^[4]. In Vivo: In primed rats, Rotigotine (N-0923) (0.035, 0.1 and 0.35 mg/kg) induces contralateral turning behavior in a dose dependent manner. In drug naive rats, the turning behavior induced by Rotigotine, either alone or in combination with SCH 39166, is reduced compared to primed rats^[3].