Rat cortex slices were incubated with 3H-dopamine (3H-DA), and the effect of desipramine (DMI) was studied on the accumulation of 3H-DA and 3H-noradrenaline (3H-NA) in the tissue and the concentrations of 3H-DA and 3H-NA in the incubation medium. This effect was compared with the effect of cocaine, reserpine and FLA 63 studied by the same technique, in order to elucidate the mechanisms of action of DMI.
All the drugs induced a significant decrease of 3H-NA accumulation in the cortical tissue. The 3H-DA retention varied: cocaine and reserpine caused a significant decrease, FLA 63 a marked, significant increase, and DMI a slight, but significant increase. In the incubation medium, 3H-DA significantly increased after DMI, cocaine and reserpine, and remained unchanged after FLA 63. In all experiments 3H-NA in the medium was very low.
It is suggested that DMI in cortex slices may exert a double mechanism of action on the final step in the noradrenaline biosynthesis: 1. an inhibition of the 3H-DA uptake at the level of the noradrenergic cell membrane, and 2. an inhibition of the intraneuronal transport of 3H-DA to sites where it is converted to 3H-NA, concomitant with an increased intraneuronal 3H-DA accumulation. Other possibilities are discussed.
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Gerlach, J., Nielsen, M. & Randrup, A. Effect of desipramine on rat cortex slices incubated with 3H-dopamine. Psychopharmacologia 37, 341–349 (1974). https://doi.org/10.1007/BF00428920
- Cortex Slices
- FLA 63