Heroin

Heroin dependence remains broadly stable. Known users are a largely ageing population with serious health, social and psychiatric problems, although indications of heroin use amongst some younger groups are noted. 

Patterns of weekend and recreational drug use increasingly involve combinations of illicit and licit drugs, including alcohol and tranquillisers. 

Heroin has a special place among the opiates, as most of our practical knowledge of drug dependence has come from experience with this drug. The behavior of heroin addicts attracts more attention than that of other drug users and is more likely to lead to crime and to committal for therapy. In most statistics, heroin users feature disproportionately in comparison to users of cannabis or benzodiazepines. Heroin users are in most cases polytoxicomanes, also using substances such as cannabis, codeine, cocaine, benzo-diazepines 

In the specific case of heroin the premature decision that heroin was not addicting cannot be considered to have been illogical. Previous information on central analgesics was restricted to morphine and codeine and the simple methylation of the phenolic hydroxyl in morphine had markedly reduced analgesic and addicting properties and had increased convulsive 

Wright first synthesized heroin, or 3,6-diacetylmorphine, from morphine in 1874. The Bayer Company of Germany advertised heroin as an antitussive in 1898. Under U.S. law (but not the laws of many other countries) heroin has no accepted medical use it is classified as a Schedule I drug under the Controlled Substances Act of 1970. 

Heroin is typically self-administered by intramuscular or intravenous injection and also by nasal insufflation ( snorting ) or smoking. Peak heroin concentrations in blood are achieved within 1 to 

5 min after intravenous and smoked administration20 and within 5 min after intranasal and intramuscular administration.28 In a study in which the method of smoked heroin delivery was optimized to reduce losses due to pyrolysis and sidestream smoke, Jenkins et al20 reported similar pharmacokinetic profiles for the smoked and intravenous routes. Mean elimination half-lives for two subjects across three doses of heroin were 3.3 and 3.6 min, after smoked and intravenous administration, respectively. The mean residence time of heroin was less than 10 min after all doses by both routes. Cone et al.28 reported that the pharmacokinetic profile of intranasal heroin was equivalent to that for the intramuscular route. Mean elimination half-lives (hours plus or minus SD) were determined to be 0.09 0.05, 0.07 0.02, and 0.13 0.07, following intranasal administration of 

6 and 12 mg, and intramuscular administration of 6 mg of heroin, respectively. The relative potency of intranasal heroin was estimated to be approximately one half that of intramuscular administration. 

The addition of two acetyl-ester groups to the morphine molecule produces a more lipophilic compound. Experimental evidence suggests that heroin and morphine may exert their effects via different receptor mechanisms.32 33 

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Morphine is the principal alkaloid of opium. It acts both as a base and as a phenol and reacts to form methylmorphine (codeine ) and diacetylmorphine (diamorphine or heroin). 

Partial synthesis is relatively unimportant in the field of alkaloid synthesis, since only a few compounds are available at low price (see table 23). An exception is the derivatization of the morphine base, which leads to codeine, heroin, and other important compounds. These trivial reactions, however, are covered in elementary text books. 

An opium alkaloid Although it is an excellent analgesic its use is restricted because of the potential for addiction Heroin is the diacetate ester of morphine )... 

Marquis reagent (gives a purple-red coloration, then violet, then blue with morphine, codeine, dionine, and heroine) mix 3 mL of concentrated H2SO4 with 3 drops of a 35% formaldehyde solution. 

Anhydride has been used for the illegal manufacture of heroin [561-27-3] (acetyknorphine) and certain other addictive dmgs. Regulations on acetic anhydtide commerce have long been a feature of European practice. After passage in 1988 of the Chemical Diversion and Trafficking Act, there is also U.S. control. Orders for as much as 1,023 kg acetic anhydtide, for either domestic sale or export, require a report to the Department of Justice, Dmg Enforcement Administration (54). 

The most common illicit dmgs ia the United States today are heroin, cocaine, marijuana, hashish, phenycHdine, LSD, and methamphetamine. These make up at least 90% of the total dmgs seized. 

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. 

Introduced in 1898, heroin was heralded as a nonaddictive alternative to morphine. Subsequent clinical experience showed it to be highly addictive and preferred by addicts over morphine (13). Heroin is approximately ten times more potent than morphine, with quicker onset and shorter duration of... 

Heroin Narcotic drugs Marijuana Cocaine Heroin Physical factors Temperarure Lightning Hypoxia Irradiation... 

Dioctyl sulfo-succinate codeine, morphine, monoacetyl-mor-phine, heroin stabilization dipping solution, 20% in ethanol [94]... 

Morphine and heroin form fluorescent oxidation products on heating in the presence of ammonia [1]. 

Note The natural fluorescence colors of some flavonoids [7, 9] and anthracene derivatives [16] are altered by the ammonia treatment. This makes possible differentiation on the basis of color. Detection limits per chromatogram zone have been reported of 2 ng for morphine and heroin [2], 6 ng for ochratoxin A [5] and 1 pg for penicillic acid [13]. 

Morphine hRf 20 — 25), 6-monoacetylmorphine hRf 35 — 40) and heroin hRf 50 — 55) appeared as blue fluorescent zones on a dark background under long-... 

Fig. 1 Fluorescence scan of a mixture of alkaloids with ca. 50 ng substance per chromatogram zone morphine (1), 6-monoacetylmorphine (2) and heroin (3).

Detection and result The chromatogram was dried in a stream of warm air for 5 min, immersed in the dipping solution for 6 s and heated to 110°C for 20 min. After drying in a stream of cold air morphine hRf 25 — 30), 6-monoacetylmorphine hR( 40-45) and heroin hRf 50-55) yielded reddish chromatogram zones and codeine hRf 30—35) yielded blue chromatogram zones on a pale pink background. 

Fig. 1 Reflectance scan (A) and fluorescence scan (B) of a mixture of alkaloids with 725 ng (A) and 100 ng (B) substance per chromatogram zone. Morphine (1), codeine (2), 6-mono-acetylmorphine (3), heroin (4).

Gianesello et al. (120) described the determination of the bronchodilator brox-aterol in plasma by on-line LC-GC. After deproteination and extraction, the LC separation was carried out by using a mixture of -pentane and diethyl ether (55 45 (vol/vol) as mobile phase. A small cut of the LC chromatogram (shown in Figure 11.9(a)) was introduced at 85 °C into the GC via so-called concurrent solvent evaporation. Figure 11.9(b) demonstrates that a detection limit of about 0.03 ng/ml was obtained. A fully automated LC-GC instrument was described by Munari and Grob (121) and its applicability was demonstrated by the determination of heroin metabo-... 

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.

F. Munari and K. Grob, Automated on-line HPLC-HRGC instnimental aspects and application for the determination of heroin metabolites in urine , J. High. Resolut. Chromatogr. Chromatogr. Commun. 11 172-176(1988). 

Methadone metabolites, methadone, cocaine (underivatized). morphine, and heroin... 

The existence of further alternative transcripts of MOP was postulated by the observation that in knockout mice with disrupted exon 1, heroin but not morphine was still analgesically active. Based on earlier observations that the antagonist naloxazone blocked morphine-induced antinociception but not morphine-induced respiratory depression, a subdivision of the MOP in pi and p2 was proposed. However, no discrete mRNA for each of these MOP subtypes has been found. It is, however, possible that subtypes of MOPs result from heterodimerization with other opioid receptors or by interaction with other proteins. 

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