Opiates endogenous compounds

If opiates are such addictive and potentially lethal compounds, why does the body respond to them As with the cannabinoids (Chapter 7), it has been discovered that the body and brain possess numerous opiate-specific receptor sites. As many as nine receptor subtypes have been identified, with three of them being the most important p (mu), k (kappa) and 8 (delta). The finding that the distribution of opiate receptors did not parallel the distribution of any known neurotransmitter prompted the search for and identification of a number of endogenous compounds specific to these receptors. These enkephalins and endorphins are manufactured within the brain and other body systems (especially the gut and intestines) and form the body s natural response to pain. They appear to be produced in bulk chains of amino acids called polypeptides , with each active neurotransmitter being composed of around five amino acid molecules. These active neurotransmitters are subsequently cleaved from the larger polypeptides at times of demand for example, it has been demonstrated that the plasma levels of these active compounds rise during childbirth, traumatic incidents and vigorous physical exercise. 

HPLC with immunoassay detection is useful for the analysis of those metabolites which are difficult to isolate from biological fluids by extraction (e.g. glucuronides). Such polar compounds cannot be observed at low concentrations with conventional detectors as they are obscured by endogenous compounds. HPLC with immunoassay detection can be applied to the determination of cannabin-oids, opiates, lysergide, and cardiac glycosides in biological fluids (A. C. Mof at,Analyl. Proc., 1981, IS, 115-116). 

Fig. 1 Capillary electrophoretic separation of opiates. Running conditions 100 mM phosphate buffer pH 6.0. Electrokinetic injection with field-amplified sample stacking after solid-phase extraction of spiked urine using double mechanism cartridges. Precision of migration times 1.2% R.S.D. (relative standard deviation), resolution >2 with all peaks shown. Within the day and day-to-day repeatability 1-4% R.S.D., respectively detection by UV at 200 nm. Peak identification pholcodine (P), MAM (6-M), heroin (H), codeine (C), morphine (M), dihydrocodeine (D), and levallorphan (I.S.) E represents an unidentified endogenous compound present in urine (see inset). (From Ref. 9 with permission.)...

The present review will focus on the behavioral consequences of two peptidergic compounds, oxytocin and vasopressin. A variety of other peptides, such as corticotropin releasing hormone (CRH), gonadotropin-hormone releasing hormone (GNRH), and the endogenous opiates, such as beta-endorphin (to name only a few) also influence behavior. 

Analogous to the discovery of the endogenous opiates and opiate receptors, the discovery of cannabinoid receptors in 1988 suggested the presence of endogenous cannabimimetic compounds. In 1992 anandamine—the ethanolamide of arachidonic acid was purified from porcine brain and shown to behave... 

Caffeine and theophylline are not the only drugs we regularly consume to block our adenosine receptors. There is also theobromine, which is found in chocolate. Chocolate is as addicting as coffee—if not more so—possibly because it contains an array of other psychoactive compounds that may contribute to the pleasurable sensation of eating it. Chocolate contains fats that may induce the release of endogenous opiates... 

During the mid-1970s the search for endogenous ligands for opioid receptors led to the discovery of peptides with opiate-like activity. The first opioid peptides reported were the pentapeptides leucine and methionine enkephalin (Sand 4) (7), followed shortly thereafter by dynorphin A (3 8) (260,261) and ( endorphin (51)(262). Because these peptides are structurally distinct from the alkaloid opiates, the term opioid was introduced to describe all compounds, both nonpeptide and peptide, with opiate-like activity. These mammalian opioid peptides share a common N-terminal tetrapeptide sequence, but differ in their C-terminal residues (Fig. 7.9). They also differ in... 

Endorphins. General term derived frrom endogenous (= originating from within) and morphine for analges-ically active peptides from the brain of mammals and man. The E. are biogenetically closely related to the enkephalins and dynorphins. Like these compounds, the E. block opiate receptors in the brain and spinal cord, thus preventing transmission of pain signals. The therapeutic use is hindered by the fact that they cannot pass the blood-brain barrier and, like synthetic opiates, cause addiction. 

When the identify of the inhibitory activity present in a sample is unknown (as is frequently the case when RRAs are used to screen for novel substances), the absolute amount of the substance cannot be determined from an RRA. Nevertheless, RRAs are useful to detect the presence of unidenhfied substances m tissue extracts, to monitor the success of purification techniques used to concentrate or isolate an unknown agent, or to detect the dilution or loss of the inhibitory activity during separation or purification attempts Even in instances when the identity of the inhibitory activity present in a sample is known, as is the case for the RRA for endogenous opiates (Childers et al., 1977, Simantov et al., 1977), the concentration of the substance may remain indeterminant, since this assay does not discriminate between the various opioid peptides that occur in brain. In either of these latter situations, the difficulty m determining the absolute amounts of the inhibitory activity present in the initial sample is circumvented by expressing the displacement of specifically bound ligand in arbitary units of equivalence relative to a reference compound. 

Morphine, C17H19NO3, is a complex phenolic compound whose pentacyclic structure is derived from tyrosine. It is analgesic, narcotic and a powerful respiratory depressant which was previously used iu cough elixirs. Morphine induces euphoria and dependency in some people, anxiety and nausea in others. The central nervous system effects occur through stimulation of specific receptors. Opiate receptors are widely distributed in animals they respond to both endogenous transmitters (peptides) and ingested plant alkaloids. The main receptor types are 8 emotional X. sedative x analgesic a psychotomimetic (Robinson 1986). 

This enzyme hydrolyses enkephalins, for example, tyr-gly-gly-phe-met or tyr-gly-gly-phe-leu, which are neuropeptides, and endogenous ligands of opiate receptors and are of importance for physiological supression of pain [75]. Compounds 59 and 60 were isolated after an Amadori rearrangement with the unprotected peptides in more than 70% yield and not only exhibited specific activity against metallopeptidases, but inhibited endopeptidase (EC 3.4.24.11) practically exclusively. 

It is common for people to experience gratifying and even ecstatic effects from eating capsaicin-flavoured foods. This attributes to pain-stimulated release of the endogenous opioid, endorphins, which have a different mechanism of action from that of the local receptor overload that makes capsaicin effective as a topical analgesic. The effect can be blocked by compounds that compete for receptor sites with endorphins and opiates." ... 

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