IVABRADINE, (-)- is an (R)-enantiomers of Ivabradine. IVABRADINE, (-)- produced a concentration-dependent block of hKv1.5 channels. S 16260 (R configuration) and S 16257 (S configuration) of Ivabradine were equipotent in reducing the spontaneous firing of rabbit sinus node preparations, but S 16260 induced significant prolongations of action potential duration of ventricular preparation (guinea pig papillary muscle and rabbit purkinje fibers), contrary to S 16257. These in vitro data have been confirmed by in vivo studies in anesthetized pigs showing the equipotence of the two isomers in reducing the heart rate, the absence of effect of S 16257 on the QT interval corrected for heart rate (QTc) in contrast with S 16260 which induced a dose-dependent increase in the QTc, indicating a direct effect on ventricular repolarization.

A-803467 is a selective NaV1.8 channel blocker with IC50 of 8 nM, blocks tetrodotoxin-resistant currents, exhibits >100-fold selectivity against human NaV1.2, NaV1.3, NaV1.5, and NaV1.7. A-803467 reduces behavioral measures of chronic pain. Systemic administration of A-803467 demonstrated acute antinociceptive activity as measured as a reduction in mechanical allodynia in several models of inflammatory and neuropathic pain in rats. Additionally, systemic and intraspinal delivery of A-803467 attenuates both evoked and spontaneous firing of wide dynamic range neurons in rats with spinal nerve ligations.

PAP-1 (5-(4-phenoxybutoxy)psoralen) is the selective inhibitor of Kv1.3, voltage-gated K+ channel, that is highly expressed in cell membranes of activated effector memory T cells (TEM). The blockade of Kv1.3 results in membrane depolarization and inhibition of TEM proliferation and function. PAP-1 is 23-fold selective over Kv1.5, 33- to 125-fold selective over other Kv1-family channels, and 500- to 7500-fold selective over Kv2.1, Kv3.1, Kv3.2, Kv4.2, HERG, calcium-activated K+ channels, Na+, Ca2+, and Cl- channels. PAP-1 does not exhibit cytotoxic or phototoxic effects, is negative in the Ames test, and affects cytochrome P450-dependent enzymes only at micromolar concentrations. PAP-1 potently inhibits the proliferation of human TEM cells and suppresses delayed-type hypersensitivity, a CD4+ T cell-mediated reaction, in rats when administered intraperitoneally or orally. PAP-1 further effectively treats allergic contact dermatitis, a CD8+ T cell-mediated reaction.

PD 173212 is a potent, selective N-type voltage-gated Ca2+ channel blocker (IC50 = 36 nM), it possesses selectivity for non L-type Ca ÷2 channels versus neuronal Na ÷, K ÷, and L-type Ca ÷2 channels. PD 173212 demonstrated potent in vitro activity in the IMR-32 assay as well as in electrophysiology, and it was efficacious in the audiogenic seizure mouse model.

Kartogenin is an activator of the smad4/smad5 pathway, and promotes the selective differentiation of multipotent mesenchymal stem cells into chondrocytes. It is promising agent for treatment of osteoarthritis.