Antiradical effects of antihistamines in human blood. Structure-activity relationship.

Pheniramines and Oxidative Burst of Blood Phagocytes During Ischaemia/Reperfusion

“…Effect of pheniramines tested on CL, indicative of oxidative burst, of whole human blood was structure-dependent and related to lipophilicity, partition coefficient and other physicochemical parameters [6]. BPA and CPA differ from PA by halogenisation of the molecule with Br-and Cl-substitution.…”

“…Blood samples (10ml) were obtained from tail vein at end of reperfusion period. Luminolenhanced CL was measured in whole blood (WB), diluted 200-times with Tyrode solution; 250 ml of diluted sample was placed in a Luminometer (LM-01 T Immunotech) for 3 600 s and evaluated as described previously [3,6]. For in vitro experiments, each pheniramine (pheniramine=PA; brompheniramine=BPA; chlorpheniramine=CPL) was used at concentrations of 10 -100 mmol/L and administered in two doses (10 mg/kg i. p. each) -before anaesthesia and before reperfusion in vivo.…”

“…Several H 1 -antihistamines (H 1 -AH) have been shown to suppress CL of blood phagocytes in vitro both extra-and intracellularly, directly as scavengers or by interacting with regulatory cell mechanisms, respectively [4,5]. Since pheniramines, a group of H 1 -AH, have been shown to suppress oxidative burst of blood phagocytes in vitro [6], the effect of pheniramines on whole blood CL was studied (i) in vitro in whole blood (WB) obtained from rats previously exposed to mesenteric ischaemia-reperfusion (I/R); (ii) on administration in vivo in the model of rat mesenteric I/R injury.…”

The effects of H1-antihistamines on the nitric oxide production by RAW 264.7 cells with respect to their lipophilicity

“…R M values provide important evidence about the lipophilicity of the drugs studied. In comparison with PHE, increased lipophilicity predisposed CPH and BPH to be better incorporated into the lipid part of the membrane and its interaction with key proteins [28]. Actually, in comparison with PHE, CPH and BPH were able to suppress nitrite production by LPS-stimulated macrophages significantly.…”

Protective effect of pheniramines against mesenteric ischaemia/reperfusion-induced injury

“…Pheniramines, a group of H 1 antihistamines, decrease free radical formation by activated neutrophils in vitro in this order: pheniramine< chlorpheniramine< brompheniramine [1]. Halogen substitution in the pheniramine molecule increases lipophilicity; compared to pheniramine, chlor-and brompheniramine possess greater lipophilicity.…”