Rotigotine hydrochloride

A non-selective agonist of the dopamine D3 receptor (Ki=0.71 nM) ; has 10-fold selectivity for the D3 receptor over the D2, D4, and D5 receptors and 100-fold selectivity for the D3 receptor over the D1 receptor; behaves as a full agonist of D1, D2, and D3 with similar potencies (EC50) in functional assay; also demonstrates significant affinity at α-adrenergic (α2B, Ki=27 nM) and serotonin receptors (5-HT1A Ki=30 nM) ; significantly attenuates MPTP-induced acute cell degeneration in mouse model.Parkinson's Disease Approved (In Vitro) :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) . 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. (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.