Morphine heroin from

P-Endorphin. A peptide corresponding to the 31 C-terminal amino acids of P-LPH was first discovered in camel pituitary tissue (10). This substance is P-endorphin, which exerts a potent analgesic effect by binding to cell surface receptors in the central nervous system. The sequence of P-endorphin is well conserved across species for the first 25 N-terminal amino acids. Opiates derived from plant sources, eg, heroin, morphine, opium, etc, exert their actions by interacting with the P-endorphin receptor. On a molar basis, this peptide has approximately five times the potency of morphine. Both P-endorphin and ACTH ate cosecreted from the pituitary gland. Whereas the physiologic importance of P-endorphin release into the systemic circulation is not certain, this molecule clearly has been shown to be an important neurotransmitter within the central nervous system. Endorphin has been invaluable as a research tool, but has not been clinically useful due to the avadabihty of plant-derived opiates. 

Figure 11.12 GC analysis of (a) urine sample spiked with opiates 3 p.g/ml) and (b) blank urine sample. Peak identification is as follows 1, dihydrocodeine 2, codeine 3, ethylmor-phine 4, moipliine 5, heroin. Reprinted from Journal of Chromatography, A 771, T. Hyotylainen et al., Determination of morphine and its analogues in urine by on-line coupled reversed-phase liquied cliromatography-gas clrromatography with on-line derivatization, pp. 360-365, copyright 1997, with permission from Elsevier Science.

In human blood, only 6-acetylmorphine was formed from heroin, with no 3-acetylmorphine or morphine being detected. Four kinetically distinct enzyme activities were seen, namely one in plasma, one in the cytosol of red blood cells, and two in red blood cell membranes [92], In human plasma at 37°, hydrolysis to 6-acetylmorphine occurs with a tm value of some minutes, the enzyme responsible being cholinesterase [90] [93]. These and other results tend to indicate that the formation of morphine from 6-acetylmorphine is due to tissue carboxylesterases, in particular cerebral enzymes [94],... 

The metabolism of heroin is of interest in connection with its pharmacological activities. Earlier opiate -receptor binding studies led to the belief that heroin is a prodrug acting through its metabolites 6-acetylmorphine and morphine [95]. However, heroin is now known to activate (5-receptors, whereas morphine activates -receptor and 6-acetylmorphine acts at both receptor types [96]. Thus, the pharmacodynamic profile of heroin results from both direct and metabolite-mediated effects. 

In 2005, global seizures were 342 mt opium (up from 212 in 2004), 32 mt morphine (down from 39 in 2004) and 59 mt heroin (60 in 2004). All opiate seizures combined (heroin, morphine and opium, as expressed in heroin equivalents1 2), amounted to 125 mt in 2005, representing a 3 per cent increase from 121 mt in 2004. 

Very simple liquid-liquid partitioning systems have been employed to isolate many drugs from biological media. Alkaloids, antihistamines, barbiturates, and tranquilizers from blood, can be extracted from urine, stomach juices, and tissue, using acetone diethyl ether, 1 1, and aqueous phases of varying pH (3-6). Typical drugs include caffeine, cocaine, atropine, codeine, heroin, morphine, quinine, doxylamine, chlorpheniramine, diphenyl-pyraline, amobarbital, pentobarbitol, secobarbitol, and pheno-barbitol (2-5). 

In a report by Nakahara et al., the extraction efficiency of various methods for 6-AM and morphine was compared. Finely cut hair samples were placed into solutions of methanol, 0.1 M HCl, methanol-5 M HCl (20 1), helicase, or methanol-trif-luoroacetic acid (TFA) (9 1). Extraction was performed overnight following ultrason-ication for 1 h, except for the methanol extract, which was sonicated for 14 h. Methanol-TFA was found to be the best solvent for extracting 6-AM and morphine with minimal hydrolysis and maximum extraction efficiency. Nakahara et al. noted that heroin was not detected in heroin users hair by this method, possibly due to hydrolysis to 6-AM. The extraction rates of 6-AM and morphine from heroin users hair with methanol-TFA reached a plateau after 8 to 10 h. 

For the purposes of investigating the disposition of heroin and its metabolites in heroin users, Goldberger et al. developed a GC/MS assay for heroin, 6-AM and morphine in biological fluids, including hair. Hair samples were obtained from subjects who had been enrolled in an outpatient maintenance and detoxification study. 6-AM and morphine were present in all samples heroin was present in 35% of the samples. Codeine was also present in 75% of the samples. The concentrations of 6-AM in hair generally predominated over those of heroin, morphine, and codeine. 

Criteria for the differentiation of heroin use from other forms of opioid exposure based upon hair analysis have been proposed by Moeller et al. Data from over 1000 hair analyses were evaluated, and the following criteria must be met in order to establish heroin use if the morphine concentration <1.0ng/mg, the morphine-to-codeine ratio must be >5 1 if the morphine concentration >1.0 ng/mg, the morphine-to-codeine ratio must be >2 1. In addition, the presence of 6-AM is definitive evidence of heroin exposure, since it can only be derived from metabolism of heroin. 

In a study of maternal drug use by Kintz and Mangin, hair samples were collected from neonates with confirmed in utero exposure to heroin. Morphine was present in all samples in a concentration range similar to previous reports based on analysis of hair from adults. Codeine was also present in aU samples, but in low concentration. Maternal hair was not tested. Urine samples were also collected and tested for opioids. Four (44%) samples were positive for morphine and 6-AM. The data indicate that drug and/or drug metabolite is transferred to the fetus through the placenta and retained in hair. 

Morphine is obtained only from the opium poppy. Ai-paver isomniferum. either from opium, the resin obtained by lancing the unripe pod. or from poppy straw. The latter pn>-cess is favored, as it helps to eliminate illicit opium from which heroin is readily produced. Morphine occurs in opium in amounts varying from 5 to 20% HJSP requires not lesi than 9.5%). It is i.solated by various methods, but the final step is usually the precipitation of morphine from on aeij solution by use of cxeess ammonia. Tltc precipitated raor-phine then is reerystallized from boiling alcohol. 

Protection of—OH VOC esters of phenols and alcohols can be prepared by standard methods, and they are readily hydrolyzed by NajCOs in aqueous dioxane, conditions that do not affect N-VOC groups. Unlike N-VOC groups, VOC esters are stable to HCl in dioxane at 25° and fairly stable to 50% aqueous HBF4. The hydrolytic selectivity is illustrated by the preparation of nalorphine, a heroin antagonist, from morphine (equation I) in 77% overall yield. 

Qpiates include heroin (obtained from morphine), morphine, and codeine. In the analysis of heroin, opium, and morphine, 5 mg of the sample should be dissolved in 1 mL... 

Chemistry The first step toward making heroin is extracting morphine from the opium plant extract. The lime method, introduced in Chapter 6, Section 6.3.3, and shown in Figure 6.8, is a common extraction protocol that yields morphine... 

Tables 18.1,18.2, and 18.3 hst concentration measurements madeatdiEferenttimes during regular classes, final exams, and the summer when few students were present, respectively. A -Tetrahydrocannabinol (THC) is the major psychoactive compound in marijuana. THC is rapidly oxidized to 11-hydroxy THC and then to ll-nor-9-carboxy-A -THC, which is the main metabolite excreted. The main metabolic route of cocaine involves the hydrolysis of ester linkages to produce benzoylecgonine (BE). 6-Acetylmorphine is the main specific metabolite of heroin (3,6-diacetylmorphine). Codeine is O3 -methylmorphine. Morphine-3 p-glucuronide is a metabolite formed in vivo by the attachment of a sngar to the O3 oxygen, which facilitates elimination of morphine from the body. All three of these morphine-based derivatives are narcotics. 3,4-Methylenedioxymethamphetamine (MDMA) and 3,4-metltylenedioxy-amphetamine (MDA) are amphetamine derivatives that are commonly referred to as ecstasy.

---