The greek god "Morpheus" was the namesake for morphine. Morpheus was the god of dreams. The chemist Serturner was the first
to publish the isolation of morphine from the opium poppy, and named this new chemical after Morpheus, presumably because
he recognized that it caused somnolence. Prior to the chemical isolation of morphine, opium had been well-established to induce
analgesia, as well as euphoria and sedation, which lead to its popularity as a recreational habit in certain cultures. The
term "opioid" refers to any drug derived from opium, or with chemical structure similar to drugs derived from opium. "Narcotic"
refers to any drug, of any class, that induces a somnolent-like state (aka narcosis), and does not specifically infer any
The most well accepted and relevant opioid receptors are mu, kappa, and delta. They are members of the transmembrane G-protein
coupled superfamily of receptors found within the CNS and other parts of the body. Opioid receptors of all 3 types have been
identified in the spinal cord dorsal horn (laminae II and III), in the medulla, hippocampus, thalamus, raphe nucleus, all
areas of the cerebral cortex, and in the periphery including joint synovial membranes, pleural membranes, etc. It has also
been shown that opioid receptors can be newly synthesized and expressed in tissues at the onset of inflammation, which renders
potential therapeutic benefits to local application of opioids in peripheral tissues. The relative percentage of opioid receptor
types and their distribution varies between species and few of the common veterinary species have been studied. In the adult
human brain, the relative percentage of mu, kappa, and delta receptors is approximately evenly divided, with 29% of cortical
receptors being mu, 34% being kappa, and 37% being delta. The relative distribution of receptor types in various species may
be one explanation for the different behavioral or analgesic effects elicited by opioids with different agonist or antagonist
activities. For example, in birds it is well established that analgesia is superior with butorphanol compared with morphine.
Because butorphanol is a kappa agonist and mu antagonist, one could speculate that birds have a higher proportion of kappa
receptors in the areas of their CNS that process information about pain.
Physiologic effects of opioid receptor activation
A drug that binds the receptor and causes a conformational change resulting in ion flux and intracellular changes is referred
to as an agonist. A drug that binds a receptor but causes no conformational change and simply blocks the receptor from binding
by other drugs is referred to as an antagonist.
Drugs that are agonists at the mu receptor result in spinal and supraspinal (CNS) analgesia, sedation in some species (primates,
dogs, exotics), euphoria, bradycardia, mild respiratory depression (except primates), ileus, constipation, nausea, vomition,
urinary retention. Kappa agonist drugs result in mild supraspinal analgesia, mild sedation. Delta agonist drugs cause dysphoria
and agitation. Thus a pure agonist drug such as morphine will have effects at all 3 receptors and the clinical result is therefore
predictable. Opioids are also classified with respect to their relative receptor affinity, with morphine being the gold standard
to which all others are compared. By definition, morphine has a receptor affinity = 1. If an opioid has a receptor affinity
= 10 (e.g. oxymorphone), this simply means that it takes 1/10th the number of molecules to elicit the same result, not that
the drug is "better" or more analgesic, just more potent. This is why morphine is typically dosed at 1.0 mg/kg and oxymorphone
at 0.1 mg/kg.
As with any drug, there will be individual variability in opioid effects and analgesia. This may be due to differences in
the intensity of pain perceived between individuals or the difference in pain tolerance in a given individual. It also may
be due to differing bioavailability of the drug depending on the patient. For example, a geriatric patient generally has a
lower volume of distribution; therefore a given dose of drug in mg/kg will result in higher plasma concentrations. A second
example is the species-specific bioavailability of oral morphine (MS Contin). In dogs there is a huge 1st pass effect, such
that therapeutic concentrations of morphine are rarely achieved, whereas in people this 1st pass effect does not occur and
therefore MS Contin is analgesic in people. There may also be differences in metabolism and clearance of the drug depending
on the species or an individual animal's renal and hepatic function. For example, in cats morphine is probably not broken
down into its glucuronide metabolites, resulting in longer circulating half-lives of the parent drug. Finally, in people at
least, there are genetic differences in opioid responsiveness: for example morphine induced respiratory depression is greatest
in the Native American Indian, followed by Caucasians, followed by Asians. These genetic differences have not been studied
in veterinary medicine, but many have observed that Northern Breeds of dogs (Husky, Malamute) become very vocal and dysphoric
after high doses of opioids and seem to do "better" when low doses are used, combined with sedation.