European Journal of Pharmacology - Volume 175/3, 1990 [antikvár]

European Journal of Pharmacology, 175 (1990) 229-235 Elsevier229EJP 51131Effects of buflomedil and its two derivatives, CRL40634 and CRL40598, on pancreatic exocrine secretion in the ratJacques Chariot, Claire Nagain, Charles Vaille and Claude RozéINSERM U 239, Faculté de Médecine Xavier Bichat, 16 Rue Henri Huchard, F-75018 Paris, France Received 9 October 1989, accepted 31 October 1989Buflomedil is a vasoactive drug used in the treatment of peripheral vascular disease, and seems to be an antagonist of both 1- and aj-vascular adrenoceptors. CRL40634 and CRL40598 are metabohtes of buflomedil and also possess vasoactive properties. The purpose of this study was to investigate whether buflomedil, CRL40634 and CRL40598 have antagonist activity on the j-^drenoceptors involved in the inhibition of exocrine pancreatic secretion. In acute pancreatic fistula rats, buflomedil, CRL40634 and CRL40598 did not suppress the inhibitory effect of clonidine against 2-deoxy-glucose-induced pancreatic secretion. However, all three drugs inhibited 2-deoxy-glucose-induced pancreatic secretion, their order of potency being CRL40598 > CRL40634 > buflomedil.Pancreatic exocrine secretion; Adrenoceptors; Buflomedil; CRL40634; CRL405981. IntroductionBuflomedil (fig 1) has been reported to be beneficial in the treatment of peripheral vascular disease. Its major pharmacological effects seem to be related to antagonism of -adrenoceptors. Buflomedil is apparently not selective for a,- or z-subtypes (Vanhoutte, 1984, Clissold at al., 1987). Two of its metabohtes, CRL40634 and CRL40598 (fig. 1), also display vascular actions that may be of potential therapeutic interest (unpublished results: French patent 78 26464). Some data suggest that these actions may to some extent be qualitatively different from those of buflomedil.Pancreatic secretion, which is potently inhibited by j-^drenoceptor agonists in the rat (Roze et al., 1981), provides an experimental model to test adrenoceptor antagonists that is differentfrom the models measuring vascular parameters. The present experiments were undertaken to test the effects of buflomedil on the inhibition of pancreatic secretion induced by clonidine, and to compare the effects of CRL40634 and CRL40598 with the effects of buflomedil in this preparation.2. Materials and methods2.1.AnimalsMale Wistar rats weighing 280-320 g were obtained from Iffa Credo, Les Oncins, F-69210 L'Arbresle, and were maintained on standard laboratory chow (UAR 113, Ahmentation Rationnelle, Villemoisson, F-91360 Epinay sur Orge).2.2.Collection of pancreatic juice and experimental schedulesCorrespondence to: C. Rozé, INSERM U239, Faculté X. Bichat, 16 Rue H. Huchard, F75018 Paris, France.The rats were deprived of food at 5 p.m. on the day before the experiment, but were allowed to0014-2999/90/$03.50 1990 Elsevier Science Publishers B.V. (Biomedical Division)