Background:

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 Ki of 0.71?nM, 4-15?nM, and 83?nM for the dopamine D3 receptor and D2, D5, D4 receptors, and dopamine D1 receptor.

Rotigotine (N-0923) has a 10-fold selectivity for D3 (pKi 9.2) receptors compared with D2, D4 and D5 (pKi 8.5-8.0) and a 100-fold selectivity compared with D1 receptors (pKi 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 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].

参考文献:
[1]. Wood M, et al. Rotigotine is a potent agonist at dopamine D1 receptors as well as at dopamine D2 and D3 receptors. Br J Pharmacol. 2015 Feb;172(4):1124-35.
[2]. Scheller D, et al. The in vitro receptor profile of rotigotine: a new agent for the treatment of Parkinson's disease. Naunyn Schmiedebergs Arch Pharmacol. 2009 Jan;379(1):73-86.
[3]. Fenu S, et al. In vivo dopamine agonist properties of rotigotine: Role of D1 and D2 receptors. Eur J Pharmacol. 2016 Oct 5;788:183-91.
[4]. Radad K, et al. Neuroprotective effect of rotigotine against complex I inhibitors, MPP and rotenone, in primary mesencephalic cell culture. Folia Neuropathol. 2014;52(2):179-86.