Luigi Rossini

Cholinergic effects of cimetidine and ranitidine

Cimetidine and ranitidine were submitted to eight in vitro assays: their intrinsic activity was evaluated on guinea-pig auricles and ileum, acetylcholine synergism on guinea-pig tracheal muscle, frog rectus abdominis, guinea-pig vas and rat phrenic nerve diaphragm, and antagonism on guinea-pig auricles and rat jejunum estimated at a range of concentrations. Ranitidine alone opposed 1-hyoscyamine antagonism in guinea-pig ileum when acetylcholine was the agonist, but not when the agonist was bethanechol.

Sodium-activated potassium current in mouse diaphragm

The mouse diaphragm muscle fiber was studied using the loose patch clamp technique. The voltage gated sodium currents were evoked by step pulses from a holding potential of about −70 mV. Following the activation of the sodium current, a very large and fast outward current was evoked. The sensitivity of this current to 4‐aminopyridine and tetraethylammonium indicates the potassium ion as the possible carrier for the channel. Furthermore, the sensitivity to tetrodotoxin and extracellular sodium demonstrated the sodium dependence of this current.

The usefulness, in pharmacological classification, of complementary pattern-recognition techniques and structure modelling as afforded by the iterative collation of multiple-trial data in data banks☆

In this emerging information age no significant limits can be envisaged to the immense resources of knowledge that pharmacological sciences can draw upon by systematically applying multivariate pattern-recognition techniques to those data banks which can be organized internationally with better standardization of descriptors, i.e. by parametrizing observations and evaluating monitoring in experimental, biological assays, clinical trials and postmarketing surveillance. Even conventionally or habitually adopted references and communalities such as traditional drug profiles and receptor models may be iteratively re-checked and suitably adapted so as to take account of more adequate, up-to-date analytical techniques, fresh biological ideas and new advances in terms of physiological refinements. An attempt may also be made to modify the chemicophysical relationships and patterns currently traced on the basis of what are held to be quantitative structure-activity oversimplifications. The present paper focuses upon specifying a number of standardization criteria in conventional assays and upon submitting multiple biological features to monitoring; in addition, it gives some picture of the new trends the approach can offer and draws attention to the more relevant, innovative literature references.

Electrophysiological analysis of the cholinergic effects of cimetidine and ranitidine

The study takes the form of an analysis of the effects of cimetidine and ranitidine (2 x 10(-4) M) on 9 electrophysiological parameters, using a single frog sciatic nerve-sartorius muscle preparation. The parameters evaluated were: (i) mean end-plate potential (e.p.p.) amplitude, and mean 50%-corrected e.p.p. amplitude, (ii) mean rise time (RT), (iii) mean half-decay (HD), (iv) mean miniature end-plate potential (m.e.p.p.) amplitude, (v) mean resting membrane potential (RMP), (vi) mean m.e.p.p. frequency (f), (vii) mean quantal content (m), (viii) quantum release probability (p), and (ix) number of active sites (n) in the nerve terminal. Marquardt analysiswas used in order to determine the effects of cimetidine and raniditine on end-plate potential kinetics. At the concentration assayed only ranitidine showed a marked blocking effect at postsynaptic level as well as a less pronounced presynaptic effect. The time course of the e.p.p.s is also more affected by raniditine, though the kinetic behaviour observed is not a unique feature of this drug alone.

Characterization of the rabbit aorta endothelium-dependent cholinergic receptor by agonist equipotent molar doses

The endothelium-dependent acetylcholine, metacholine, carbachol, betanechol, and furtrethonium relaxation values have been measured in vitro for the rabbit aorta, in presence of a high concentration of hexamethonium. The produced EPMR values complete the values that were obtained in a previous experiment under analogous conditions for rat bladder, ileum, iris, stomach, and trachea preparations. The complete set was analyzed by new statistical techniques of data analysis and display, which are both simpler and more precise than the statistical modeling techniques used by us in the past. This has led to new results concerning the clustering of drugs and of receptors, as well as to a characterization of the endothelium receptor.