Stabilization of the T-state of ferrous human adult haemoglobin by chlorpromazine and trifluoperazine

In the present study, the effect of the neuroleptics chlorpromazine (2-chlo ro-N,N-dimethyl-10H-phenothiazine-10-propanamine) and trifluoperazine {10-[ 3-(4-methylpiperazin-1-yl)-propyl]-2-(trifluoromethyl)-10H-phenothiazine} o n the EPR-spectroscopic properties of ferrous human adult nitrosylated haem oglobin (HbNO) is reported. Addition of the two drugs to HbNO shifted the c onformational equilibrium from the high- to the low-affinity form of the li gated tetramer, as observed for 2,3-D-glycerate bisphosphate, the physiolog ical modulator of haemoglobin action. The effect of chlorpromazine and trif luoperazine on the EPR-spectroscopic properties of HbNO was enhanced by ino sitol hexakisphosphate. The binding of neuroleptics to ferrous human adult haemoglobin may represent an important undesirable side effect. In fact, ox ygen affinity for ferrous human adult haemoglobin decreases on increasing c hlorpromazine and trifluoperazine concentration, In addition, red blood cel ls may act as neuroleptic scavengers.