Receptors peripheral opiate

Peripheral opiate receptors have be n identified in the ileum and are responsible for the antidiarrhoeal activity of opiates. If peripheral sensory nerves also possess opiate receptors, drugs might be designed versus these sites and as a result would not need to cross the blood-brain barrier. 

Peterson PK, Sharp BM, Gekker G, Jackson B, Balfour HH Jr (1991) Opiates, human peripheral blood mononuclear cells, and HIV. Adv Exp Med Biol 288 171-178 Peterson PK, Gekker G, Schut R, Hu S, Balfour HH Jr, Chao CC (1993) Enhancement of HlV-1 replication by opiates and cocaine the cytokine connection. Adv Exp Med Biol 335 181-188 Peterson PK, Gekker G, Hu S, Sheng WS, Molitor TW, Chao CC (1995) Morphine stimulates phagocytosis of Mycobacterium tuberculosis by human microglial cells involvement of a G protein-coupled opiate receptor. Adv Neuroimmunol 5 299-309 Peterson PK, Molitor TW, Chao CC (1998) The opioid-cytokine connection. J Neuroimmunol 83 63-69... 

The actions of all clinically used opiates can now be explained in terms of their acting as agonists at one of the four opiate receptors found in the brain, spinal cord and peripheral nervous system. All four receptors are inhibitory (Table 21.2). 

There are a number of side-effects of opiates that are due to their actions on opiate receptors outside the central nervous system. Opiates constrict the pupils by acting on the oculomotor nucleus and cause constipation by activating a maintained contraction of the smooth muscle of the gut which reduces motility. This diminished propulsion coupled with opiates reducing secretion in the gut underlie the anti-diarrhoeal effect. Opiates contract sphincters throughout the gastrointestinal tract. Although these effects are predominantly peripheral in origin there are central contributions as well. Morphine can also release histamine from mast cells and this can produce irritation and broncho-spasm in extreme cases. Opiates have minimal cardiovascular effects at therapeutic doses. 

Findings continue to accumulate in the field of endogenous opiates, as exemplified by two tetrapeptides isolated from mammalian brain and found to have high affinity and selectivity for p-opioid receptors. These tetrapeptides are endomorphin-1 (Tyr-Pro-Trp-Phe-NH2) and endomorphin-2 (Tyr-Pro-Phe-Phe-NH2). A number of synthetic analogues have been prepared with the view to improve their metabolic stability and, in some cases, to limit their access to peripheral opioid receptors. The three synthetic endomor-phin analogues Tyr-D-Ala-Phe-Phe-NH2 (6.84), Tyr-D-Arg-Phe-Phe-NH2 (6.85), and Tyr-D-Arg-Phe-Ape-NH2 (6.86), to be discussed in the next section, have potent antinociceptive effects in in vivo inflammatory tests but exhibit modest effects in the CNS. However, and despite the presence of a D-amino acid and a protected C-terminus, they remained sensitive to enzymatic hydrolysis [211][212],... 

It is worth mentioning that iV-allylic substitution in a number of morphine derivatives, as a rule, leads to antagonistic properties. Naloxone is a few times stronger than nalorphine as an antagonist. It blocks opiate receptors. It eliminates central and peripheral action of opioids, including respiratory depression. Naloxone is used upon overdose of narcotic analgesics.Synonyms for this drug are narkan, talwin, and others. 

There are many peripheral organs that possess enkephalin opiate receptors the ileum, the most distal part of the small intestine, and the vas deferens are the most significant. The receptors in the ileum are responsible for the antidiarrheal activity of opiates. This is also the explanation for the severe constipation that may occur when people use opiates for pain relief. 

Opiates produce constipation by affecting receptors in the intestines. Opium extracts were used in this capacity to treat diarrhea. Today there are other related compounds on the market which accomplish the peripheral task without affecting the CNS because of their poor absorption from the Gl tract when taken orally. Imodium A-D , an OTC, contains loperamide. It is also available as a generic OTC. The prescription mixture of diphenoxylate and atropine is called Lomotil . 

Pharmacological studies with selective agonists have shown that opioid control of intestinal electrolyte transport is predominantly mediated by delta opioid receptors [58], while the gastrointestinal propulsion is under the control of mu receptors [59,60]. The antidiarrheal effects of NEP inhibitors, such as acetorphan, the prodrug of thiorphan, have been compared to those of an opiate agonist, loperamide, in a model of castor oil-induced diarrhea in rats. When administered peripherally, they produced a delayed onset of diarrhea with no reduction in the gastrointestinal transit [61,62], as is commonly observed with loperamide [63],... 

Wiister, M., Schulz, R., and Herz, A. 1981. Multiple opiate receptors in peripheral tissue preparations. Biochem. Pharmacol. 30, 1883-1887. 

Bechara A, Van der Kooy D (1987) Kappa receptors mediate the peripheral aversive effects of opiates. Pharmacol Biochem Behav 28 227-233... 

Giordano J, Rogers L (1989) Peripherally administered serotonin 5-HT3 receptor antagonists reduce inflammatory pain in rats. Eur J Pharmacol 170 83-86 GUck SD, Crane LA (1978) Opiate-like and abstinence-like effects of intracerebral histeimine administration in rats. Nature 273 547-549... 

Codeine is an opioid analgesic that stimulates opiate receptors in the CNS also causes respiratory depression, peripheral vasodilation, inhibition of intestinal perstalsis, stimulation of... 

Fentanyl is an opioid analgesic that is a potent, short-acting, rapid-onset opiate agonist that relieves pain by stimulating opiate receptors in the CNS also causes respiratory depression, peripheral vasodilation, inhibition of intestinal peristalsis, sphincter of Oddi spasm, stimulation of chemoreceptors that cause vomiting, and increased bladder tone. 

Hydrocodone bitartrate is an opioid analgesic combination that inhibits synthesis of prostaglandins, binds to opiate receptors in CNS, and peripherally blocks pain impulse generation produces antipyresis by direct action on the hypothalamic heat-regulating center causes cough suppression by direct central action in the medulla and may produce generalized CNS depression. They are indicated in the management of mild to moderate pain. 

Hydrocodone bitartrate/chlorpheniramine maleate is an anti-tussive combination. Hydrocodone suppresses cough reflex stimulates opiate receptors in the CNS and peripherally blocks pain impulse generation. Chlorpheniramine competitively antagonizes histamine at H,-receptor sites. They provide relief of cough and rhinorrhea and symptomatic relief of stubborn cough and runny nose caused by cold or allergy. 

Hydrocodone bitartrate/homatropine methylbromide is an antitussive combination. Hydrocodone suppresses the cough reflex stimulates opiate receptors iu the CNS and peripherally blocks pain impulse geueratiou. Atropine inhibits action of acetylcholine or other cholinergic stimuli at postgauglionic cholinergic receptors. They are used for symptomatic relief of cough. 

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