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.