Mechanism of Tissue-Selective Drug Action in the Cardiovascular System

Table 3.

Selective Drugs? Antiarrhythmic and Pharmacological Profiles

Properties	RSD1000	RSD 1019	Lidocaine
^a The in vivo profile involved testing the compounds for effectiveness against ischemia-induced arrhythmias in anaesthetized animals as well as testing for effects on blood pressure, heart rate, and ECG. Therapeutic ratios were estimated from the dose-response curves for antiarrhythmic activity versus effects on the ECG and/or blood pressure.
^b The in vitro profile was obtained in isolated perfused rat hearts or isolated myocytes.
^c The “ischemic” selectivity ratios were calculated from dose response curves for indices of sodium channel blockade obtained at pH 7.4 and 6.4. Larger ratio values represent greater ischemia-selectivity. The data were taken from Bain et al. (17) and Yong et al. (18).
In vivo profile^a
Antiarrhythmic ED₅₀ (μmole/kg/min)	2.5±0.3	2.8±0.4	5.4±1.8
Therapeutic ratio (versus cardiovascular depression)	10	12	9
Convulsive dose (μmole/kg/min)	32	32	32
In vitro profile^b
Kv4.2 block IC₅₀ (μM)		6.6±1.4
Kv1.5 block IC₅₀ (μM)	2.8±0.1	3.6±0.3
Na block IC₅₀ (μM)	2.9±0.3
“Ischemic”-selectivity^c for ion channel block	40	70