The effect of methyl paraben on tracheal smooth muscle in vitro

The widely used bacteriostatic preservative methyl paraben (M.P.) produced a concentration-dependent relaxation of the carbachol-contracted guinea pig trachea and the isolated rabbit jejunum. The relaxant effects on the trachea were not blocked by dl-propranolol and the responses on the rabbit jejunum were not blocked by bretylium tosylate which abolished the responses to sympathetic nerve stimulation. Sub-threshold concentrations of M.P. (130 muM) produced a marked and significant enhancement of the responses of the trachea to the three catecholamines dl-isoprenaline (I), 1-noradrenaline (N), 1-adrenaline (A), a slight but significant enhancement of the responses of the trachea to the two non-catechol beta sympathomimetics salbutamol (S), and orciprenaline (O), but no significant enhancement of the responses to aminophylline (AM). It is concluded that the relaxant effect of M.P. is characteristic of a "non-specific" spasmolytic and this is consistent with its reported local anaesthetic activity. In addition, the specific ability of M.P. to enhance responses to catecholamines suggests that it may be interacting with a mechanism responsible for catecholamine removal (i.e., tissue uptake or uptake 2). In view of the widespread use of M.P. in pharmaceutical preparations in concentrations often equivalent to or greater than those employed in the present investigation, the fact should be stressed that its presence should not be overlooked in the interpretation of experimental and clinical studies.