Picenadol.
Picenadol is a unique opioid mixed agonist-antagonist analgesic currently under clinical evaluation. Structurally, picenadol is a 4-phenylpiperidine derivative and a racemic mixture whose mixed agonist-antagonist properties are a consequence of the d-isomer being a potent opiate agonist, whereas the l-isomer is an opioid antagonist. In the mouse writhing and rat tail heat tests, the analgesic potency of picenadol is estimated to be 1/3 that of morphine. Picenadol itself has weak antagonist activity, whereas the antagonist potency of the l-isomer is approx. 1/10 that of nalorphine. Evaluation of picenadol's affinity for opioid receptors reveals that picenadol, unlike other mixed agonist-antagonists has high affinity for both the mu and delta receptors but a markedly lower affinity for the kappa receptor. Extensive pharmacological investigations show picenadol to have a low potential to produce opiate-like side effects, including a low liability for abuse and physical dependence.
Zimmerman
D M
DM
Smits
S E
SE
Hynes
M D
MD
Cantrell
B E
BE
Leander
J D
JD
Mendelsohn
L G
LG
Nickander
R
R
D000818:Animals; D055598:Chemical Phenomena; D002621:Chemistry; D010856:Columbidae; D004285:Dogs; D004361:Drug Tolerance; D005260:Female; D006168:Guinea Pigs; D008297:Male; D051379:Mice; D009020:Morphine / Q000037:antagonists & inhibitors; D009043:Motor Activity / Q000187:drug effects; D009270:Naloxone / Q000494:pharmacology; D010146:Pain / Q000188:drug therapy; D010880:Piperidines / Q000494:pharmacology* / Q000627:therapeutic use / Q000633:toxicity; D051381:Rats; D011919:Rats, Inbred Strains; D011976:Receptors, Muscarinic / Q000187:drug effects; D017981:Receptors, Neurotransmitter / Q000187:drug effects; D011957:Receptors, Opioid / Q000187:drug effects; D017478:Receptors, Phencyclidine
D010880:Piperidines; D011976:Receptors, Muscarinic; D017981:Receptors, Neurotransmitter; D011957:Receptors, Opioid; D017478:Receptors, Phencyclidine; D009270:Naloxone; D009020:Morphine; C035115:picenadol