Copyright© 1995, by Ballh6re Tmdall All rights of reproduction m any form reserved
Schedule 2'
Schedule 3:
Schedule 4:
Batlhbre's Chntcal Anaesthestology-Vol 9, No 1, March 1995 ISBN 0-7020-1849-X
Dezocine (p) Meptazinol
cr
Pentazocme Butorphanol Nalbuphine
Bold= newer agomsts/antagonlsts, p = partial agonlst
NEW AGONIST/ANTAGONIST ANALGESICS
85
particularly numerous in the cortical areas of the brain, the spinal cord, and the periaqueductal grey matter, where they affect the input and/or pathways for the interpretation of pain (Itzhak, 1988; Pasternak, 1988). The analgesia and side effects of the agomst/antagonists are mainly a function of which of these receptors are stimulated or inhibited, and to what extent. The current theory of opioid drug action involves at least three opiate receptors (Snyder, 1984). More have been suggested, most notably a specific receptor for [3-endorphin called eplsllon (e) In addition, subtypes of receptors, Ix1 and Ix2, K1 and K2, have been suggested. In our discussion of the agonists/ antagonists, we concentrate on the three most widely studied receptors, ix, g, and K. We also examine the cr receptor, but th~s ~s probably not a true opiate receptor, since actions mediated by this receptor are not reversed by naloxone The receptors, associated pharmacodynamics, agonists, and antagomsts are summarized in Table 1. As can be seen from Table 1, the ix, 8, and K receptors all are assocmted with analgesia, and all of the agonists/antagonists stimulate one or more of these receptors to some degree. It is the extent to which the (r receptor is stimulated that determines many of the unwanted side effects of this group of drugs. The newer drugs in the class of agonists/antagonists are dezocine, meptazinol, and ciramadol. Chemical structures are shown in Figure 1. Table 2 presents brand names, morphine equivalence, and duration of action of the common intravenous doses of agonists/antagonists. Newer drugs are included in bold face. Table 3 summarizes pharmacokinetic data available for the new drugs as well as the old. Table 4 summarizes the clinical effects and side effects of the agomsts/antagonists. Dezocine is currently available for clinical use in the United States and Europe; meptazlnol and clramadol are available elsewhere, but not available in the Umted States.
