Morphine endogenous opioid peptides

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. 

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. 

Natsuki, R. and Dewey, W. L. Changes in the levels of several endogenous opioid peptides in dog cerebrospinal fluid following morphine administration, Japanese Journal of Alcohol and Drug Dependence 1993, 28, 379-394. 

The structures of the endogenous opioid peptides were larger than that of morphine (Fig. 2). The upper row of Fig. 2 depicts dynorphin, which shows moderate selectivity for the tc receptor. Enkephalin also shows moderate selectivity for the S receptor. Its structure is the portion of the dynorphin structure ending at dashed line b. The two peptides possess a common seg-... 

In the 1970s, Hughes et al. were the first to show that two very different chemical structures have similar agonist properties (3). The opioid natural product, morphine (3), was found to resemble the N-terminal structure of the endogenous opioid peptides, enkephalins, (4a) and (4b), and j3-endorphin (5) (Fig. 15.2). The remarkable similarity between the morphine phenol system and the IV-terminal tyrosine residue in the peptide opioids implied that these units reacted with opioid receptors in a similar fashion to elicit comparable responses (4-6). 

Endogenous opioid peptides (endorphins, dynor-phins, enkephalins), have been termed the brain s own morphine. Their discovery in 1972 explained why the brain has opioid receptors when there were no opioids in the body. These peptides attach to specific opioid receptors, mainly p (mu), 5 (delta) or K (kappa) located at several spinal and multiple supraspinal sites in the CNS. Opioid receptors are part of the family of G-protein-coupled receptors (see p. 91) and act to open potassium channels and prevent the opening of voltage-gated calcium channels which reduces neuronal excitability and inhibits the release of pain neurotransmitters, including substance P. 

Endogenous opioid peptides are increased in myocardial ischemia. Their effect is mediated through presynaptic and postsynaptic mechanisms. Opioids limit the release of stimulating catecholamines by its presynaptic action while opioid receptor agonists act via Gi -linked pathways postsynaptically and alter myocardial channel activity and intracellular activities of protein kinases. Table 1. Figure 10. Blockade of 5 and x-opioid receptors reduced the tolerance of the isolated rabbit heart to ischemia and reperfusion.105 Furthermore, blockade of 8-opioid receptor abrogated the ischemic preconditioning mediated cardioprotective effect while activation of 8-opioid receptor by morphine decreased infarct size and apoptosis in a rabbit model of coronary occlusion and reperfusion.106... 

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