Opioids extraction

Natural opioids, that is, opioids extracted directly from opium include codeine—used for dental and other postoperative pain laudanum, paregoric—a mild tincture of opium mixed with camphor and used primarily for control of diarrhea and morphine. Heroin is a partial synthetic that combines morphine and diacetyl... 

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."... 

A 17 amino acid long peptide sequentially related to opioid peptides in particular dynorphin A. OFQ/N is inactive at the 5, k, and p opioid receptors, but binds to its own NOP receptor (formerly ORL-1, for opioid receptor like-1). In contrast to opioid peptides, OFQ/N has no direct analgesic properties. OFQ/N is the first example for the discovery of a novel neurotransmitter from tissue extracts by using an orphan receptor as bait. Centrally administered in rodents, OFQ/N exerts anxiolytic properties. OFQ/N agonists and antagonists... 

Morphine, when extracted from raw opium and treated chemically, yields the semisynthetic narcotics hydromorphone, oxymorphone, oxycodone, and heroin. Heroin is an illegal narcotic in the United States and is not used in medicine. Synthetic narcotics are those man-made analgesics with properties and actions similar to the natural opioids. Examples of synthetic narcotic analgesics are methadone, levorphanol, remifen-tanil, and meperidine Additional narcotics are listed in the Summary Drug Table Narcotic Analgesics. 

Immunochemical methods have been reported for the determination of these substances in body fluids (see Table 8) in clinical and forensic analyses. In the case of illicit use of opioid drugs, methods have also been reported for the control of drug abuse and assessment of intoxication using body fluids, tissue extracts, post-mortem specimens, and seizure samples. For this reason there are several commercially available immunochemical methods (see Table 4). 

MOR were comparable (10 ng mL4), whereas those for DHC and EMOR were about fourfold lower. Furthermore, glucuronides were shown to react like the corresponding free opioids. Validation with real urine samples was performed with identification of the peaks by capillary electrophoresis-ion-trap mass spectrometry (CE-MS) after solid-phase extraction. 

Ca2+ channels Ginseng extract rapidly and reversibly inhibits high-threshold, voltage-dependent Ca2+ channels in micromolar doses (Nah and McCleskey 1994 Nah et al. 1995). This effect is mediated by a receptor linked to a pertussis toxin-sensitive G protein, but it is not through o2 adrenergic, GABAB, muscarinic, or opioid receptors (Nah and McCleskey 1994). Several ginsenosides inhibit Ca2+ currents by 16 to... 

Opioid A recent study has shown activity of hypericum extracts at opioid receptors (Simmen et al. 1998). Extracts displace naloxone from p and x opioid receptors in the micromolar range (IC50 25 and 90 pg/ml, respectively). In contrast, extracts of the sedative herb Valeriana officinalis do not have this effect. This effect is due to unidentified constituents and not by the flavonoids quercetin or kaemferol. Opioids are known to have effects on emotion, so it is conceivable that activity of hypericum at p and k receptors contributes to its therapeutic effects (Gerra et al. 1998 Tejedor-Real et al. 1995 Walker and Zacny 1998). Although they are not conventional treatment for depression, opioids such as buprenorphine have been effective in treatment of refractory depression (Bodkin et a. 1995). However, for any further conclusions to be drawn, it would be necessary to further e uddate the opioid effects of hypericum to determine what functional effect, if any, hypericum has on the receptors. 

Finally, a thorough receptor binding study by Raffa and colleagues (1998) showed that hypericin extracts had no effect at adrenergic (alpha or beta), adenosine, angiotensin, benzodiazepine, dopamine, bradykinin, neuropeptide Y, PCP, NMDA, opioid, cholecystokinin A, histamine HI, or nicotinic ACh receptors. Although comprehensive, this study did not look at the binding of any other hypericum constituents. 

Nah SY, McCleskey EW. (1994). Ginseng root extract inhibits calcium channels in rat sensory neurons through a similar path, but different receptor, as mu-type opioids. J Ethnopharmacol. 42(1) 45-51. Nah SY, Park HJ, McCleskey EW. (1995). A trace component of ginseng that inhibits Ca2+ channels through a pertussis toxin-sensitive G protein. Proc Natl Acad Sci USA. 92(19) 8739-43. 

Dams R, Benijts T, Lambert WE, De Leenheer AP. 2002. Simultaneous determination of in total 17 opium alkaloids and opioids in blood and urine by fast liquid chromatography-diode-array detection-fluorescence detection, after solid-phase extraction. J Chromatogr B Analyt Technol Biomed Life Sci 773(1) 53-61. 

Progress in the molecular characterization of opioid receptors has been slower than for other cell-surface receptors and, to date, none has been sequenced or cloned and the second messengers mediating opioid actions are still unknown. The literature in this area has been reviewed in 1990 by Lo and Smith [11], who cite three main problems with the opioid receptor it is difficult to solubilize, there are no simple biochemical assays to test the functional integrity of an isolated receptor extract and there are at least three receptor subtypes (designated as mu, kappa and delta). 

Figure 7.6 Structure of remifentanil and its major metabolite formed by ester hydrolysis. contrast, alfentanil has an intermediate hepatic extraction (0.3-0.5) and alfentanil clearance will be sensitive to changes in both liver blood flow and reduced enzyme capacity in patients with liver disease. Although the kidneys play a minor role in the elimination of most opioids, renal disease can influence their pharmacokinetic profile, secondary to alterations in plasma proteins and intra- and extravascular volumes. Neither the pharmacokinetics nor the pharmacodynamics of remifentanil is significantly altered in patients with liver or renal disease.

Most drugs used in anaesthesia are metabolised in the liver by phase I reactions, mediated by cytochrome P-450 enzymes. These are susceptible to destruction by cirrhosis, so that the biotransformation of drugs, such as opioids (except morphine), benzodiazepines, barbiturates, and inhalational agents, may be markedly altered in severe liver disease. These enzymes are found in the centrilobular areas, which are more prone to hypoxia. In contrast, the enzymes responsible for phase II reactions, found predominantly in the peripheral areas, often function normally even in advanced disease. The disposition of benzodiazepines that are eliminated primarily by glucuronidation, e.g. lorazepam and oxazepam, are unaffected by chronic liver disease. For drugs with low hepatic extraction, advanced hepatocytic dysfunction decreases phase I and II biotransformation with a reduced clearance and prolongation of the elimination half-life. This is often partially offset by an increased free fraction due to decreased protein binding. 

While morphine as a component of opium has been in use for centuries and the first synthetic opioid, pethidin, was prepared as early as 1939, opioid peptides, the endogenous pentapeptides Met- and Leu-enkephalin (YGGFM and YGGFL), were identified in brain extracts only in 1975 by Kosterlitz and Waterfield (Hughes et al., 1975 also see Cox et al., 1975 Hughes, 1975 Lord et al., 1977). 

Stevia Stevia rebaudiana) Uses Natural sweetener, hypoglycemic and hypotensive properties Actions Multiple chemical components sweetness d/t glycoside, stevioside hypotensive effect may be d/t diuretic action or vasodilation action Available forms Liq extract, powder, caps Notes/SE HA, dizziness, bloating Interactions T Hypotensive effects W/ antihypertensives esp CCB, diuretics EMS Monitor BP does not encourage dental caries may -1-glucose St. John s Wort (Hypericum perforatum) Uses Mild-mod depression, anxiety, anti-inflammatory, immune stimulant/anti-HIV/antiviral, gastritis, insomnia, vitiligo Action MAOI in vitro, not in vivo bacteriostatic bactericidal, T capillary blood flow, uterotonic activity in animals Efficacy Variable benefit w/ mild-mod depression in several trials, but not always seen in clinical practice Available forms Teas, tabs, caps, tine, oil ext for topical use Dose 2-4 g of herb or 0.2-1 mg of total hypericin (standardized extract) daily Notes/SE Photosensitivity (use sunscreen) rash, dizziness, dry mouth, GI distress Interactions Enhance MAOI activity, EtOH, narcotics, sympathomimetics EMS T Risk of photosensitivity Rxns t effects of opioids and sympathomimetics... 

Hydromorphone and its natural opioid relatives have been used to relieve pain, treat a variety of ailments, and create euphoric feelings at least as far back as the time of the ancient Greeks. In early Greek history, the priests controlled the use of opium and ascribed to it supernatural powers. In the fifth century bc, Hippocrates, the father of medicine, dismissed the supernatural attributes of opium. Hippocrates believed opium had cathartic, narcotic, hypnotic, and styptic properties. He believed that all diseases had a natural origin and could be cured by natural therapies. All of the natural opiates historically were derived from opium poppy plants. The liquid extracted from the poppy seeds was typically dried to create a concentrated powder. These extracts were then smoked, eaten, or drank. 

Morphine has a strong analgesic effect and has been used for the alleviation of postoperative and cancer pain since antiquity, but its use is now restricted because of its drug dependency. Morphine and its homologues were called opiates after opium, which was extracted from poppy seeds. This class of drugs are now termed opioids. 

Other effects observed in vitro include opioid sigma receptor binding using the hypericin fraction and GABA receptor binding using the commercial extract. Interleukin-6 production is also reduced in the presence of the extract. 

Deltorphins are endogenous linear heptapeptides, isolated from skin extracts of frogs belonging to the genus Phyllomedusa, that have a higher affinity and selectivity for delta opioid-binding sites than any other natural compound known [36]. Two deltorphins with the sequence Tyr-Ala-Phe-Asp (or Glu)-Val-Val-Gly-NH2 have been identified and well characterized [36]. 

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