Picenadol

Abstract

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.

Development of κ Opioid Receptor Antagonists

“…106–112 All N -substituted analogues, including the N -methyl analogue ( 17 , R = CH 3 ), were pure antagonists. 110,111,113,114 As a strategy for obtaining a potent and selective κ opioid selective N -substituted trans -3,4-dimethyl-4-(3-hydroxyphenyl)piperidine analogue, a library of compounds based on the general structure 18 was synthesized.…”

Chiral Mesoporous Silica Materials: A Review on Synthetic Strategies and Applications

“…Take ofloxacin, for instance; it is a fluoroquinolone antibiotic against both gram-negative and gram-positive bacteria, and levorotatory ofloxacin exerts superior pharmacological activity than the dextral form. Picenadol is an opioid mixed agonist-antagonist for the relief of pain, whose d -optical isomer acts as an opioid agonist, while the l -isomer is an opioid antagonist [ 102 ]. Another example is that thalidomide was a major teratogen that caused birth defects in the 1960s.…”

Chiral Drugs and the Associated Asymmetric Synthesis

“…Picenadol (14) is a unique opioid mixed agonist-antagonist analgesic currently under clinical evaluation. The (þ)-isomer of picenadol is a potent opiate agonist, whereas the (À)-isomer is an opioid antagonist (Zimmerman et al, 1985). (c) All the pharmacological activity may reside in one enantiomer; in this case the other enantiomer may be regarded as an impurity.…”