Empirical atom atom potential calculations on two antagonist on histamine H2 receptors: ranitidine and etintidine

ENRIZ R D; G.M CIUFFO; M.R.ESTRADA; E.A.JAUREGUI

ACTA CIENTIFICA VENEZOLANA

Asociación Venezolana para el Avance de la Ciencia

Lugar: Caracas; Año: 1988 vol. 39 p. 214 - 223

0001-5504

Empirical atom-atom potential calculations for ranitidine andetintidine have been made,in order to show the behaviour of the speciesin solution at 37 ºC. It has been assumed that hydration should eliminateelectrostatic interactions and consequently, calculations are performedon molecules without charges. For both molecules, very rigidand· folded conformations (4 = ± 60°) was obtained, with a populationof 95 per cent for ranitidine and 65 per cent for etintidine, whichshow a remarkable parallelism between the planes of the ring andthe "cyanoguanidine equivalent" group. When the different configurationalisomers was co8Jf ed, ranitidine showed the confi~urationalisomer (Z,E ip10 - 1 , as the mo-st important isomer, with a 97per cent of the .whole population, whereas_for etintidine, the most populatedisomer was the E,Z 1P10 = 0° (95 %- 97%). This kind of conformationfound in ranitidine and etintidine was very similar to thosefound previously for cimetidine and metiamide, and we propose thatthese conformations are the adequated for the interaction with the receptor,'since the distances between potentially active groups of about3.5 A and 4.5 A have been found. This distances would be importantfor the recognition on the H2-histamine receptors.