synthesis and anti-inflammatory performance of newly cyclizine derivatives on adult male wistar rats

cyclizine (1-benzhydryl-4-methyl-piperazine, cas 82-92-8, cyc, i), a piperazine derivative, belongs to h1 antihistamine group of drugs that shows such pharmacological properties as anti-inflammatory, anti-allergic and anti-platelet effects, similar to other h1-receptor antagonists. in this study, two new tolyl and cumene derivatives of i (1-ethyl-4-[(p-isopropylphenyl) (p-tolyl) methyl]-piperazine, ii and 1-[3, 4-dichlorophenyl]-4-[[p-isopropylphenyl] [p-tolyl] methyl]-piperazine, iii) were synthesized to investigate their acute and chronic anti-inflammatory activities in formalin and histamine-induced rat paw edema. in addition, the vascular permeability in formalin and histamine-induced paw edema, xylene-induced ear edema, and peritonitis due to acetic acid application into peritoneal cavity were measured. the cotton pellet-induced granuloma model was chosen for inducing chronic inflammation in rats. findings proved reduction in formalin-induced rat paw edema and vascular permeability (acute inflammation) by i and ii at 30 min after the injection. in addition, results in histamine-induced rat paw edema showed anti-inflammatory effects of all drugs started 60 min after the injection as these effects continued for a longer period by ii and iii comparing to i, as discussed above. in addition, the data on vascular permeability in xylene-induced ear edema and acetic acid-induced to peritoneal cavity confirmed that substitutions on cyclizine molecule were more effective and could decrease the vascular permeability and acute inflammation. however, the results from the cotton pellet-induced granuloma formation in rats revealed that none of the drugs (i-iii) were effective to reduce the reactions and intermediates of chronic inflammation.