| Description | AZD-1305 is a novel anti-arrhythmic compound that primarily blocks the fast component of IKr, l-type calcium currents and intra-ward sodium currents in mammalian cells and ventricular cardiomyocytes and can be used in studies to reverse arrhythmias. |
| In vitro | AZD1305 (0.1–30 µM, n = 6, each concentration applied for 3 min ; dog cardiomyocytes) concentration-dependently blocked INalate (IC50=4.3 microM) and INapeak (IC50=66 microM). In PFs, E-4031, but not AZD1305, markedly prolonged APD90 (from 380+/-15 to 597+/-86 ms, P<0.05) after the long CL and augmented APD90 instability (2+/-0.4 to 24+/-6.1 ms, P<0.05), increases significantly attenuated by AZD1305 and lidocaine.[3] |
| In vivo | AZD1305 ((36g/kg/min intravenously for 30 minutes ; anesthetized mongrel dogs) respectively increased QT and RR intervals from 290±7 to 397±15 ms (+37%, P<0.0001) and from 603±22 to 778±32 ms (+29%, P=0.002) at normal sinus rhythm. AZD1305 increased the QT interval from 535±28 to 747±36 ms (+40%, P<0.0001). AZD1305 slightly slowed the idioventricular rhythm.[2] |
| Target activity | Inalate:4.3 microM, Inapeak:66 microM |
| Synonyms | UNII-CZO834LXQM, AZD 1305 |
| molecular weight | 434.5 |
| Molecular formula | C22H31FN4O4 |
| CAS | 872045-91-5 |
| Storage | Powder: -20°C for 3 years | In solvent: -80°C for 1 year |
| Solubility | DMSO: 25 mg/mL (57.54 mM) |
| References | 1. Sigfridsson K, et al. Preformulation evaluation of AZD1305, an oxabispidine intended for oral and intravenous treatment. Drug Dev Ind Pharm. 2012 ; 38(1):19-31. 2. Johnson DM, et al. Reduced ventricular proarrhythmic potential of the novel combined ion-channel blocker AZD1305 versus dofetilide in dogs with remodeled hearts. Circ Arrhythm Electrophysiol. 2012 ; 5(1):201-209. 3. Andersson B, et al. The combined ion channel blocker AZD1305 attenuates late Na current and IKr-induced action potential prolongation and repolarization instability. Europace. 2010 ; 12(7):1003-1010. 4. Burashnikov A, et al. AZD1305 exerts atrial predominant electrophysiological actions and is effective in suppressing atrial fibrillation and preventing its reinduction in the dog. J Cardiovasc Pharmacol. 2010 ; 56(1):80-90. |