HOMOBENZOMORPHAN COMPOUNDS WITH A POTENT NARCOTIC ANTAGONIST PROPERTY

Abstract

In consequence of testing antagonistic activity on morphine-induced analgesia and respiratory depression of the 2’-hydroxy-6, l0-dimethy-7, 8-homobenzo-morphans, it was found that the order of antagonistic activity is N-cyclopropylme-thyl (trans isomer TA-414 and cis isomer TA-576) > N-allyl (trans isomer TA-412) > N-dimethylallyl (trans isomer TA-4I3 and cis isomer TA-4I5) with respect to the influence of replacing antagonistic substitution on the tertiary nitrogen. The properties of TA-414 and TA-576 in this regard were higher than those of nalorphine but slightly less than levallorphan. Moreover, the narcotic antagonist action of TA-414 was of long duration, comparable to that of nalorphine. On the other hand, TA-414 was entirely lacking an agonistic (analgesic) activity even at large doses, while TA-576 equalled nalorphine and pentazocine in the potency of agonistic activity in mice. Conclusively, TA-414 appears to fall under the category of a pure antagonist such as naloxone.