Ian Craig Carlyle

The neuromuscular and autonomic blocking activities of pancuronium, Org NC 45, and other pancuronium analogues, in the cat

Twenty‐six mono‐or bis‐quaternary salts of 3,17‐dioxy‐2β,16β‐dipiperidino‐5α‐androstanes (including pancuronium) and one 17‐desoxy congener were tested for neuromuscular blocking and autonomic blocking activities in the chloralose‐anaesthetized cat. The 17β‐acetoxy series, all the members of which contain an acetylcholine‐like fragment in the steroidal D‐ring, was most selective for effecting neuromuscular blockade. The salient member of this series is 3α,17β‐diacetoxy‐2β,16β‐dipiperidino‐5α‐androstane 16β‐N‐monomethobromide (Org NC 45) which is highly selective in blocking neuromuscular transmission in that a dose approximately sixty times greater than the neuromuscular blocking dose was required to block responses to vagal stimulation. In contrast, in doses sufficient to produce neuromuscular block, pancuronium simultaneously blocked responses to vagal stimulation. Moreover, pancuronium and Org NC 45 exhibited the same order of neuromuscular blocking activity and therefore the latter potentially represents a useful addition to the armamentarium of neuromuscular blocking agents currently in clinical use.

Discovery and SAR of org 24598-a selective glycine uptake inhibitor.

The discovery of Org 24598, one of the first potent and selective inhibitors of the glycine transporter is discussed. In vitro structure-activity relationships (SARs) data for interaction of a ligand with this system is discussed.