A spirohydantoin derivative of oxymorphone: an agonist with delayed antagonist activity.
We have synthesized a novel derivative of oxymorphone, oxymorphone-6 alpha-spirohydantoin. The derivative was less toxic in mice than the parent compound and it showed a significant anticonvulsive activity. It exerted agonist effects in doses lower than those of morphine and its agonist effects were longer lasting. Furthermore, both oxymorphone and the 6-spirohydantoin showed definite antagonist properties 48 hr later: they prevented analgesic effects of morphine. The antagonist effects of the derivative persisted for a week.
Alexander
G J
GJ
New York State Psychiatric Institute, New York State Office of Mental Health, New York 10032.
Chatterjie
N
N
Wisniewski
H M
HM
D000698:Analgesia; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004353:Drug Evaluation, Preclinical; D006827:Hydantoins / Q000138:chemical synthesis / Q000494:pharmacology*; D004091:Hydromorphone / Q000031:analogs & derivatives*; D008297:Male; D051379:Mice; D009020:Morphine / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D010111:Oxymorphone / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D010146:Pain / Q000503:physiopathology*; D012684:Sensory Thresholds / Q000187:drug effects; D013997:Time Factors
D000927:Anticonvulsants; D006827:Hydantoins; C061292:oxymorphone-6-spirohydantoin; D009020:Morphine; D010111:Oxymorphone; D004091:Hydromorphone