Morphine endogenous opioids

Evidence soon emerged that the endogenous opioids were peptides rather than simple morphine-like molecules (9). The first direct evidence for endogenous opioids in brain extracts was provided in 1975 when two pentapeptides were purified that differed only in the carboxyl terminal amino acids (10) (Table 1). These peptides were called methionine- (Met-) and leucine- (Leu-) enkephalin, from the Greek term meaning "in the head."... 

Similar to endogenous opioids, opiates like morphine and other synthetic opioids activate G-protein-coupled receptors which couple to G-proteins of the Gi/0 family. 

When Montgomery and I published our article, we thought we had disproven another theory of placebo effects - the theory that placebo effects are produced by the release of endorphins in the brain. In 1978 researchers at the University of California in San Francisco discovered that when placebos reduce pain, they may stimulate the release of endorphins.18 Endorphins, the existence of which had only been discovered a few years earlier, are opioids that are produced naturally by the brain. Just like the opiates that are derived from opium - morphine and codeine, for example - endorphins reduce the sensation of pain. The University of California researchers reasoned that if placebos can mimic the effects of opiate drugs, maybe they do so by stimulating the release of the brain s endogenous opioids. 

Pugh G Jr, Smith PB, Dombrowski DS, Welch SP. (1996). The role of endogenous opioids in enhancing the anti nociception produced by the combination of delta 9-tetrahydrocannabinol and morphine in the spinal cord. J Pharmacol Exp Ther. 279(2) 608-16. 

Nalorphine and levallorphan are examples. For example in patients with postoperative pain the analgesic effects of 10 mg of nalorphine is about the same as 10 mg of morphine. On the other hand naloxone and naltrexone seem to have no agonistic activity and some antagonistic affinity for all types of opioid receptors. Although antagonists could be expected to have effects by altering the actions of endogenous opioid peptides mostly such effects are not discernable. 

A series of peptides, occurring naturally in brain and possessing pharmacological properties similar to those of morphine, have been described. At least three separate families of peptides have opioid properties (Table 24.2), and the different classes of peptides reside in separate distinct neurons. It is likely that the endogenous opioid peptides coexist in neurons with other nonopioid neurotransmitters. The initial hope that these endogenous agents or synthetic derivatives of them would be found to retain the analgesic activity of the opioids but be devoid of respiratory depression and/or addictive properties has now somewhat abated. 

Ketorolac (Toradol) is an NS AID with very mild antiinflammatory and antipyretic activity. It is a potent analgesic for postoperative pain. Its efficacy is equivalent to that of low doses of morphine in the control of pain. For this reason it is often combined with opioids to reduce opioid dose and related side effects while providing adequate pain relief. It is also used to replace the opioids in some patients with opioid sensitivity. The mechanism of action of ketorolac involves the inhibition of COX and decreased formation of prostaglandins. However, some evidence exists that ketorolac may stimulate the release of endogenous opioids as a part of its analgesic activity. 

Opium is the milky exudate obtained by incising the unripe seed capsule of the poppy plant Papaver somniferum and morphine is the most important alkaloid of opium. Morphine produces analgesia through action in the brain and spinal cord, that contain peptides possessing opioid like pharmacological action. These endogenous substances are known as endogenous opioid peptides (earlier known as endorphin now known as P-endorphin). 

It is N-allyl analogue of oxymorphone, have a high affinity for mu receptor and lower affinity at delta and kappa sites. It selectively antagonizes the respiratory depression produced by opioids. After intravenous administration, it antagonizes all actions of morphine. It also blocks the actions of endogenous opioid peptides. 

Opioid alkaloids (eg, morphine) produce analgesia through actions at receptors in the central nervous system (CNS) that contain peptides with opioid-like pharmacologic properties. The general term currently used for these endogenous substances is endogenous opioid peptides. 

Homeostatic regulation of body temperature is mediated in part by the action of endogenous opioid peptides in the brain. This has been supported by experiments demonstrating that administration of -opioid receptor agonists such as morphine administered to the anterior hypothalamus produces hyperthermia, whereas administration of agonists induces hypothermia. 

Morphine interacts with the endogenous opioid system... 

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