Actions of Opioids on Targets Other Than Opioid Receptors
Recent progress in molecular pharmacologic analyses has shown
that opioids can interact with molecules other than opioid receptors. In cardiac
myocytes, it was shown that morphine can inhibit voltage-dependent Na+
current in a naloxone-insensitive manner, suggesting the existence of a signal transduction
mechanism that is not dependent on the opioid receptors.[38]
Meperidine has been classified as an agonist of both μ- and κ-receptors.
In addition, it was demonstrated that meperidine can block voltage-dependent Na+
channels in amphibian peripheral nerves[39]
as well
as in the Xenopus oocyte expression system ( Fig.
11-4
).[40]
Furthermore, meperidine exerts
agonist
Figure 11-4
Meperidine blocks the Na+
channels similarly
to lidocaine. Na+
currents induced by voltage jump were recorded from
Xenopus oocytes expressing the Na+
channels.
Lidocaine (LID; A) and meperidine (MEP; B)
dose-dependently inhibited the current. (From Wagner LE 2nd, Eaton M, Sabnis
SS, Gingrich KJ: Meperidine and lidocaine block of recombinant voltage-dependent
Na+
channels: Evidence that meperidine is a local anesthetic. Anesthesiology
91:1481–1490, 1999.)
activity at the α2B
adrenoreceptor subtype.[41]
Yamakura and colleagues have shown that high concentrations of opioids, including
meperidine, morphine, fentanyl, codeine, and naloxone, directly inhibit the N-methyl-D-aspartate
(NMDA) receptor expressed in Xenopus oocytes.[42]
It remains to be clarified whether these actions of opioids on
targets other than the opioid receptor have physiological and/or clinical implications.
