Curariform Activity and Chemical Structure.

PRELIMINARY STUDIES ON THE VENOM OF THE MARINE SNAIL CONUS*

“…I n others the exact cause of death is unknown, as in the cases of human fatality reported (Kohn, 1958). However, the responses are in general similar to those from curariform drugs (Craig, 1948). The toxic manifestations suggest the main action of the venom is interference with neuromuscular transmission, although the possibility of an action on the central nervous system cannot be excluded.…”

“…N-methylpyridinium is known to possess curariform activity (Craig, 1948). Although injection of 14'-methylpyridinium, homarine, and gamma-butyrobetaine separately into Uca pugilator did not induce paralysis (Welsh and Prock, 1958), these authors postulated possible toxicity of a mixture of bases.…”

Functional Derivatives of Sterically Hindered Amines: Piperazine diesters

“…The measured molecular weight 1230 (VPO) was in excellent agreement with the calculated value 1280, and the IR and 'H NMR spectra are in accordance with the proposed structure. The synthesis of the diethylester of (7,15-diazadispiro-[5,1,5,3]hexadecan-l5-yl)propanedioic acid (7a) and the similar compound (7b) was accomplished by nucleophilic replacement of 7,Wdiazadispiro [5,1,5,3] hexadecane 6 with the corresponding a-bromo-or a,a'dibromosubstituted aliphatic dicarboxylic acid esters (Scheme 3).…”

“…The potassium salt of 14,16-dioxo-7,15-diazadispiro [5,1,5,3] hexadecane 2 was prepared from 1 (2.50 g, 0.01 mol) and potassium hydroxide (0.56 g, 0.01 mol) by gentle heating in 25 ml of dry methanol for 0.5 hour, followed by evaporation of the solvent and reaction water, and drying on a vacuum line. Potassium salt 2 was dispersed in dry DMF (30 ml), and diethylester of 2-bromopropanedioic acid (2.39 g, 0.01 mol) in dry DMF (10 ml) was added dropwise at 80 OC during 1 hour.…”

Hexamethonium.

“…but looking back at its development 30 years later, at a time when we think a lot about how medical research is best facilitated and supported, it might be interesting to go back over the very beginnings, for any lessons to be learnt, and to see, as far as one can, where events might have taken a different and less useful course. Perhaps I should stress that a different course was very possible: four of the methonium series, as we now call it, up to pentamethonium (which is hardly distinguishable from hexamethonium), were listed, in a major review (Craig, 1948) as having 'only weak pharmacological actions'; and I doubt if any planner, or computer survey, would have picked them out for study. There is some interest, too, in the fact that it was a non-industrial development.…”