RESUMEN
The synthesis and pharmacological profiles of some new steroidal mono- and bisquaternary ammonium derivatives have been described. The compounds featured have been conceptually derived structurally from two lead structures: pancuronium bromide 1 and chandonium iodide 2. In vitro and in vivo neuromuscular blocking studies have indicated the monoquaternary compound 15 to be less active than the bisquaternary compounds 10 and 11. The compound 11 has been found to be more active than d-tubocurarine.
Asunto(s)
Bloqueantes Neuromusculares/síntesis química , Animales , Unión Competitiva , Carbacol/antagonistas & inhibidores , Gatos , Pollos , Agonistas Colinérgicos/metabolismo , Antagonistas Colinérgicos/síntesis química , Antagonistas Colinérgicos/farmacología , Músculos/efectos de los fármacos , Bloqueantes Neuromusculares/farmacología , Esteroides/síntesis química , Esteroides/farmacologíaRESUMEN
Steroidal quaternary ammonium compounds 12 and 13 with quaternised nitrogen at positions 3 and 16 of the steroidal nucleus in androstane series were synthesised and their neuromuscular blocking activities and ganglion blocking activities were studied using chick biventer and anaesthetised cat as the models. The bisquaternary compounds 12 and 13 have been found to be greater in potency than D-tubocurarine. Acetoxy derivative 13 has been found to be more potent than pipecuronium bromide taking D-tubocurarine as the standard compound indicating the need of acetoxy function at position 16.