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15686-91-6Relevant articles and documents
2 Acylaminopyridine derivatives having agonistic and antagonistic activity to morphine
Hiltmann,Hoffmeister,Niemers,Schlichting,Wollweber
, p. 584 - 600 (2007/10/04)
A search for potent analgesic substances with low abuse potentials yielded N (1 methyl 2 piperidinoethyl) N (2 pyridyl)propionamide fumarate (propiram fumarate). This compound has no chemical relationship to morphine and has morphine antagonistic as well as morphine agonistic properties. Of the derivatives of propiram tested for their analgesic efficacy, the compounds having a high analgesic potency, with a favorable therapeutic index were those in which the piperidine ring had been replaced by an azabicyclic group, the larger ring of which was a 6 or 7 membered ring. Regarding activity and toxicity, the morphine antagonistic and morphine agonistic effects of particularly interesting substances were investigated. Slight to moderate morphine antagonism was established in a number of propiram derivatives. Like propiram, these substances also have morphine agonistic properties and thus are considered partial agonists. Compounds of nalorphine type, i.e. mainly potent morphine antagonists, have not been found. A few moderately to highly effective propiram derivatives, e.g. phenyl substituted derivatives or derivatives containing an azabicyclic group, showed distinct morphine agonistic properties. These properties were in some cases very pronounced with weak or no morphine antagonism.