High- and low-affinity [3H]desipramine-binding sites in human postmortem brain tissue.

The binding of [3H]desipramine to human brain tissue was characterized. Competition studies in the frontal cortex and hypothalamus revealed a single-site binding model for noradrenaline (Ki 120-190 microM). The noradrenaline uptake inhibitors nisoxetine, nortriptyline and desipramine fitted two-site binding models and these compounds exhibited 10-80 times lower Ki values than the serotonin uptake inhibitor citalopram. The high-affinity component of the nisoxetine-sensitive [3H]desipramine binding (Ki 50-110 nM) approximated the binding sensitive to noradrenaline. This binding fraction was defined as that sensitive to 1 microM nisoxetine and showed a maximum binding capacity (Bmax) of 380 +/- 80 fmol/mg protein and an apparent Kd of 5.1 (4.5-5.7) nM in the hypothalamus. The binding was also investigated in 25 additional brain regions without finding detectable amounts of binding. However, when the specific binding was defined as that sensitive to 100 microM nisoxetine, low-affinity binding where Bmax and Kd were not possible to determine was obtained in all brain regions investigated. It is concluded that [3H]desipramine binding to human brain tissue represents multiple binding sites. Only when regarding binding sensitive to noradrenaline and to the high-affinity component of noradrenaline uptake inhibitors is the binding saturable and of high affinity. It is possible that this site represents the uptake site for noradrenaline.