The defibrillating effect of catecholamine reuptake inhibitors.
In previous studies we hypothesized that spontaneous termination of ventricular fibrillation (TVF) requires a high cardiac catecholamine level ([CA]) during VF. During VF, sympathetic activity is enhanced but in the majority of cases [CA] does not reach the level required for self-defibrillation, most likely due to their relatively high reuptake by sympathetic nerve terminals. One possibility of obtaining TVF is by elevation of the [CA] during VF, either by catecholamine intracoronary injection or by treatment with compounds that inhibit catecholamine reuptake. To examine this assumption, we studied the effect of VF on 3 closely related compounds: talopram, talsupram and citalopram, with norepinephrine uptake inhibition (IC50NE) of 2.9, 0.79 and 8800 and dopamine (DA) uptake inhibition (IC50DA) of 44000, 9300 and 41000, respectively, as well as 2 enantiomers of a cis-1-piperazino-3-phenylindan derivative (Lu20-037 and Lu20-036) with IC50NE of 2.5 and 910 and IC50DA of 2.3 and 1700, respectively. The results support our hypothesis relating the defibrillating effect of a compound to its IC50NE, while its inhibitory effect on DA uptake seems to conteract the NE effect.
Falkin
L
L
Department of Physiology, Tel Aviv Medical School, Israel.
Varon
D
D
Erez
M
M
Neuman
M
M
Manoach
M
M
Bøgesø
K P
KP
D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D002415:Cats; D015283:Citalopram / Q000627:therapeutic use*; D005260:Female; D008297:Male; D013876:Thiophenes / Q000627:therapeutic use*; D014693:Ventricular Fibrillation / Q000188:drug therapy*
D000928:Antidepressive Agents; D013876:Thiophenes; D015283:Citalopram; C001750:talsupram