Verapamil and its analogue D-600 have been found to inhibit the uptake of serotonin, dopamine, norepinephrine and choline into rat forebrain synaptosomes. The concentrations of verapamil required for 50% inhibition of the four uptake systems were 2.3 μM, 18μM, 32μM and 150μM, respectively. The inhibitory effect of verapamil on serotonin uptake was studied in detail and found to have a very rapid (less than 1 min) time of onset and an almost equally rapid rate of reversal. Inhibition appeared to be non-competitive with respect to substrate concentration. The inhibitory effects of verapamil did not seem to be due to its ability to block Ca++ movements since serotonin uptake was not dependent on Ca++ but actually inhibited by elevated Ca++, and the inhibition of uptake by verapamil could not be reversed by elevation of Ca++. However, due to an increased potency of verapamil at lowered Na+ concentrations, the Na+-dependency of the uptake processes, and verapamil's known effects on 'slow' Na+ currents, we propose that verapamil may be interfering with a Na+-dependent component of the uptake systems.
|Original language||English (US)|
|Number of pages||9|
|State||Published - Dec 1 1979|
ASJC Scopus subject areas
- Molecular Medicine