| dc.description.abstract | 1. A series of compounds in which the N
methyl group of pethidine was replaced - by
tertiary amino alkyl and alkyloxyalkyl groups,
both carrying a further ether oxygen function,
alkyloxyalkyl and aryloxyalkyl groups - has
been tested for analgesic activity in rats.
2. The method used for determining the anal ...
gesic effect was that of Green and Young {1951)
as modified by Millar and Stephenson (1956).
3. A design for a cross~over test is described.
4. Acute and subacute toxicity tests have
been performed.
5. The effects of the more active derivative
have been studied on the respiration of the
rat. Whilst the order of potency was the
same as found in the analgesic tests, the
difference in potency relative to TAl was not so
marked. TA48 is seven times more powerful
than TAl as an analgesic but only twice as
active as a respiratory depressant.
6. Structure and relationship is discussed.
7. The effect of the more active test analgesics
have been studied on the peristaltic
reflex of guinea-pig ileum. The results of
the test analgesics on this reflex ran parallel
to their relative analgesic potencies.
8. Many substances were found to be more
active than pethidine. One of these, TA48,
N-(tetrahydrofurfuryl oxyethyl) 4--phenyl-4-ethoxycarbonyl piperidine is twenty to fifty
times more potent than pethidine and is less
than three times as toxic.
9. Some of these derivatives, TA24, TA27,
TA28, TA33 and TA48, have been selected as
suitable for clinical trials. | en |
