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Stabilization of the T‐state of ferrous human adult haemoglobin by chlorpromazine and trifluoperazine
Author(s) -
Paolo Ascenzi,
Alberto Bertollini,
Massimo Coletta,
Antonio Lucacchini
Publication year - 1999
Publication title -
biotechnology and applied biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.468
H-Index - 70
eISSN - 1470-8744
pISSN - 0885-4513
DOI - 10.1111/j.1470-8744.1999.tb00911.x
Subject(s) - trifluoperazine , phenothiazine , chlorpromazine , chemistry , ferrous , stereochemistry , promethazine , tetramer , biochemistry , pharmacology , enzyme , biology , calmodulin , organic chemistry
In the present study, the effect of the neuroleptics chlorpromazine (2‐chloro‐ N , N ‐dimethyl‐10H‐phenothiazine‐10‐propanamine) and trifluoperazine {10‐[3‐(4 ‐ m e t h y l p i p e r a z i n ‐ 1 ‐ y l) ‐ p r op y l ] ‐ 2 ‐ (t r i f l u o r o m e t h y l) ‐10H‐phenothiazine} on the EPR‐spectroscopic properties of ferrous human adult nitrosylated haemoglobin (HbNO) is reported. Addition of the two drugs to HbNO shifted the conformational equilibrium from the high‐ to the low‐affinity form of the ligated tetramer, as observed for 2,3‐D‐glycerate bisphosphate, the physiological modulator of haemoglobin action. The effect of chlorpromazine and trifluoperazine on the EPR‐spectroscopic properties of HbNO was enhanced by inositol hexakisphosphate. The binding of neuroleptics to ferrous human adult haemoglobin may represent an important undesirable side effect. In fact, oxygen affinity for ferrous human adult haemoglobin decreases on increasing chlorpromazine and trifluoperazine concentration. In addition, red blood cells may act as neuroleptic scavengers.