THE INTESTINAL ABSORPTION OF SOME OMEGA-HALOALKYLAMINES AND THEIR QUATERNARY ANALOGUES

¹ Department of Pharmacology and Experimental Therapeutics, Boston University School of Medicine, and Smith Kline & French Laboratories, Philadelphia, Pennsylvania

The degree of intestinal absorption of several cyclizable omega-haloalkylamines and their corresponding quaternary analogues has been investigated and compared in the rat. Two omega-chloroalkylamines, analogues of pentolinium, were found to cyclize completely, in vitro, within 30 minutes and were not significantly better absorbed than pentolinium itself. Two omega-haloalkylamines, which cyclize in vitro within 1 hour and 2 hours to form the piperidinium analogues of pentolinium, were absorbed 57% in 3 hours compared to 14% in 3 hours for their corresponding pre-formed quaternary compound.

Indirect evidence that cycization does take place, following administration, at rates directly related to the rates of cyclization determined in vitro has also been obtained. The data, although not definitive, point to the conclusion that potentially it should be possible to synthesize compounds that cyclize slowly enough in the gut to be well absorbed, but rapidly enough in the system to produce useful pharmacologic effects.