Morphine-like agonists

When allergies occur with one opioid, a drug from a different structural class of opioids may be tried with caution. For these purposes, the mixed agonist/antagonist class behaves most like the morphine-like agonists. 

Phenanthrenes (morphine-like agonists) Morphine (various) Naturally occurring ++ +... 

The guinea-pig ileum test has been developed [242, 243] to provide quantitative data upon the agonist and antagonist properties of morphine-like drugs. The agonist activity is measured by the concentration of drug which causes 50 per cent depression of the twitch induced by coaxial stimulation (IDso value) and the antagonist activity by the equilibrium constant (A)g). The latter is obtained... 

Pure morphine-like opioid agonists in general act on p- and K-receptors. 

In experimental horses, a-methylfentanyl induces locomotive responses (as quantified by counting the number of footsteps taken per unit of time), indicating that it is a morphine-like narcotic agonist in horses. The maximum effect can be seen 10 min after treatment of horses with greater than 4 pg kg body weight. 

In animal models, these k agonists had potent antinociceptive effects and could eliminate the undesirable side effects of morphine-like drugs. They all had very similar structures that included the N-C-C-Nfv/ 2) pharmacophore sequence (shaded parts in Fig. 4), because they were derived from U-50,488H. Moreover, they lacked the tyrosine moiety that is essential for opioid activity from the viewpoint of endogenous opioid chemistry (Fig. 5). 

Nalbuphine hydrochloride (nubain) is used to produce analgesia. Because it is an agonist-antagonist, administration to patients who have been receiving morphine-like opioids may create difficulties unless a brief drug-free interval is interposed. The usual adult dose is 10 mg parenterally every 3 to 6 hours this may be increased to 20 mg in nontolerant individuals. 

The CNS effects produced by pentazocine generally are similar to those of the morphine-like opioids, including analgesia, sedation, and respiratory depression. The analgesic effects of pentazocine are due to agonistic actions at K opioid receptors. Higher doses of pentazocine (60-90 mg) elicit dysphoric and psychotomimetic effects these effects may involve activation of supraspinal K receptors and sometimes are reversed by naloxone. 

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