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Pharmacological evaluation of benzotriazole derivatives structurally related to trazodone
266
Pharmacological
Research, Vol. 26, Supplement 1, I992
CYCLOOXYGENASE ACTIVITY OF HAEMOGLOBIN:A COMPARATIVE STUDY IN DIFFERENT SPECIES Zilletti L.,Gentilini G .,Franchi-Micheli S.,Mugnai S.,Ciuffi M.:Valoti M., Moneti G.:Fusi F.$Sgaragli G., Dipartimento di Farmacologia,Universit5 di F% renze e*Istituto di Scienze Farmacologiche,Universita di Siena In a previous study we have shown that peroxidases (horseradish peroxidase and bovine lactoperoxidase EC 1.11.1.7.) catalyse the formation of prostaglandins from arachidonic acid in vitro.This property is shared by some haemeproteins including haemoglobin (l).More recently we have characterised this enzymatic activity for human haemoglobin (2). With the aim of verifying the possible cyclooxygenase activity of haemoglobins of different species,through the conversion of arachidonate to PG-like substances,we have performed a comparative study on haemoglobins from non-human mammals,fowls and reptiles.The enzymatic activity was evaluated by bioassay and mass-spectrometric analysis . (1) Zilletti L.,Ciuffi M.,Moneti G.,Franchi-Micheli S.,Valoti M.,SgaragliG. Peroxidese catalysedformaticnofprosteglsndins fmnarachidcnic acid(1939)Biochem.Pharmac01.38:2424-2439. (2) Zilletti L.,Gentilini G.,Franchi-Micheli S.,Valoti M.,Fusi F.,Ciuffi M.,i%neti G.,Sgarqli G.,Cycloaxygenase activity ofhaenoglcbin,In :Methods inEnqnology,inpress.
PHARMACOLOGICAL EVALUATION OF BENZOTRIAZOLE DERIVAWS STRUCTURALLY RELATBD TO TRAZGDONB. E.Perissutti, R.Meli*, S.Maggetti*, GCaliendo, BCappello, CSilipo, A.Vittoria, R.Di Carlo* Dept. of Pharmaceutical and Toxicological Chemistry and *Dept. of Experimental Pharmacology, University of Naples “Fcderico II” Various benzotiazole derivatives structurally related to trazodone and showing the following general formula:
were prepared and pharmacologically evaluated with in v&m and in ti rrlvo tests. Preliminary data were obtained by studymg anti-adrenergic activity on rat vas deferens, anti-histamine activity on guinea pig ileum, anti-serotonin activity on rat stomach strip, and analgesk activity by writhing test in mice. The synthesized compounds were compared for activity with tmzodone and in many cases were found to be as active as trazodone itself. By comparing the activities of the l- substituted betuotriazolea with those of the corresponding 2- isomers it seemed that the l- isomers were generally more potent, all other factors being equal. Moreover, pharmacological data showed that activity ls modulated by the length of the methylene chain and by the position of the X-substituent on the aromatic ring close to the piperazine moiety.
Pharmacological
Research, Vol. 26, Supplement 1, I992
CYCLOOXYGENASE ACTIVITY OF HAEMOGLOBIN:A COMPARATIVE STUDY IN DIFFERENT SPECIES Zilletti L.,Gentilini G .,Franchi-Micheli S.,Mugnai S.,Ciuffi M.:Valoti M., Moneti G.:Fusi F.$Sgaragli G., Dipartimento di Farmacologia,Universit5 di F% renze e*Istituto di Scienze Farmacologiche,Universita di Siena In a previous study we have shown that peroxidases (horseradish peroxidase and bovine lactoperoxidase EC 1.11.1.7.) catalyse the formation of prostaglandins from arachidonic acid in vitro.This property is shared by some haemeproteins including haemoglobin (l).More recently we have characterised this enzymatic activity for human haemoglobin (2). With the aim of verifying the possible cyclooxygenase activity of haemoglobins of different species,through the conversion of arachidonate to PG-like substances,we have performed a comparative study on haemoglobins from non-human mammals,fowls and reptiles.The enzymatic activity was evaluated by bioassay and mass-spectrometric analysis . (1) Zilletti L.,Ciuffi M.,Moneti G.,Franchi-Micheli S.,Valoti M.,SgaragliG. Peroxidese catalysedformaticnofprosteglsndins fmnarachidcnic acid(1939)Biochem.Pharmac01.38:2424-2439. (2) Zilletti L.,Gentilini G.,Franchi-Micheli S.,Valoti M.,Fusi F.,Ciuffi M.,i%neti G.,Sgarqli G.,Cycloaxygenase activity ofhaenoglcbin,In :Methods inEnqnology,inpress.
PHARMACOLOGICAL EVALUATION OF BENZOTRIAZOLE DERIVAWS STRUCTURALLY RELATBD TO TRAZGDONB. E.Perissutti, R.Meli*, S.Maggetti*, GCaliendo, BCappello, CSilipo, A.Vittoria, R.Di Carlo* Dept. of Pharmaceutical and Toxicological Chemistry and *Dept. of Experimental Pharmacology, University of Naples “Fcderico II” Various benzotiazole derivatives structurally related to trazodone and showing the following general formula:
were prepared and pharmacologically evaluated with in v&m and in ti rrlvo tests. Preliminary data were obtained by studymg anti-adrenergic activity on rat vas deferens, anti-histamine activity on guinea pig ileum, anti-serotonin activity on rat stomach strip, and analgesk activity by writhing test in mice. The synthesized compounds were compared for activity with tmzodone and in many cases were found to be as active as trazodone itself. By comparing the activities of the l- substituted betuotriazolea with those of the corresponding 2- isomers it seemed that the l- isomers were generally more potent, all other factors being equal. Moreover, pharmacological data showed that activity ls modulated by the length of the methylene chain and by the position of the X-substituent on the aromatic ring close to the piperazine moiety.