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PubMedDate not supplied

Characterization and identification of 6 mutagens in opium pyrolysates implicated in oesophageal cancer in Iran.

Previous epidemiological studies have indicated an association between the ingestion of opium pyrolysates, dietary deficiencies, and a high incidence of oesophageal cancer in subjects in north-east Iran. Laboratory studies have shown that pyrolysates of opium and particularly of morphine, a major opium alkaloid, are highly mutagenic in bacteria and induce sister-chromatid exchanges in mammalian cells after metabolic activation. We now report the ability of these pyrolysates to transform Syrian hamster embryo cells in culture and present some evidence for their carcinogenicity in mice and hamsters following topical, subcutaneous, intratracheal and intragastric administration. 6 of the most abundant mutagenic compounds present in morphine pyrolysate were isolated and purified by high-performance liquid chromatography and characterized by gas chromatography/mass spectrometry and 1H-Fourier transform nuclear magnetic resonance spectroscopy. These hitherto unknown compounds, all containing a hydroxy-phenanthrene moiety, were identified as: 3-methyl-3H-naphth[1,2-e]indol-10-ol; 1,2-dihydro-3-methyl-3H-naphth[1,2-e]indol-10-ol; 6-methylaminophenanthren-3-ol; 2-methylphenanthro[3,4-d] [1,3]oxazol-10-ol; 2,3-dimethyl-3H-phenanthro[3,4-d]imidazol-10-ol and 2-methyl-3H-phenanthro[3,4-d]imidazol-10-ol. Mutagenicity in Salmonella typhimurium TA98 of these compounds increased in the order listed, the last compound being 35 times more active than benzo[a]pyrene. The mechanisms, by which these mutagens are formed and metabolically activated are discussed.

Animals↗
PubMed1979

Assay of major and minor constituents of opium samples and studies of their origin.

Samples of opium from different countries as well as from various regions of India were studied for their morphine and codeine content by gas-liquid chromatography (GLC) as their silyl ethers in a single step. Non-phenolic alkaloids (thebaine, papaverine and narcotine) were extracted with dichloromethane for GLC after conversion of the meconic acid, morphine and codeine in opium into insoluble salts with lime water. The data on alkaloidal constituents have been utilised in a determination of the origin of seized opium samples in this preliminary study.

Alkaloids↗
PubMed2005

Therapy of the neonatal abstinence syndrome with tincture of opium or morphine drops.

BACKGROUND: Treating opioid-addicted women with methadone in pregnancy increased the number of newborns suffering from neonatal abstinence syndrome (NAS). High-pitch crying, insomnia, tremor, myoclonic jerks, vomiting, diarrhoea and poor weight gain were reported symptoms, which were evaluated using the Finnegan (F)-score. Earlier phenobarbital or paregoric had been used to suppress symptoms. We surveyed the administration of pure mu-agonist morphine (MO) in comparison to the alcoholic opioid mixture in tincture of opium (TO). Thirty-three newborns were included in the survey, after informed consent by their parents. RESULTS: NAS started 3-5 days after delivery and lasted for 27 or 30 days (mean) in the TO and MO groups, respectively. In either of the tested parameters, we found no significant differences between the two groups (2P < 0.05). The maximum F-score was similar in both groups, but the dose to suppress NAS was higher in the MO group (0.6-0.5 mg/day; total dose 61.6-42.7 mg of morphine). The duration of the therapy was longer in the MO than in the TO group (37.5-32.4 days). On the other hand the weight gain was better in the MO group than in the TO group (25-19 g/day), but was reduced in both groups compared with healthy newborns. CONCLUSIONS: Morphine is suitable to treat NAS in a similar manner as tincture of opium, but avoids unwanted effects of the alcoholic extracts with various alkaloids in the tincture of opium and allows better weight gain of the newborns.

Double-Blind Method↗
PubMed1999

The price elasticity of opium in Taiwan, 1914-1942.

Between 1895 and 1945, the Japanese colonial government virtually eliminated opium use in Taiwan by licensing and treating existing users, prohibiting sales to others, and raising the price. We evaluate these policies using a two-part model to describe the fraction of the population using opium and consumption among users, and the rational addiction model by Becker et al. (1991). We confirm that opium is addictive and find no evidence supporting the rational addiction hypothesis. Demand is price-elastic with estimated short- and long-run demand elasticities of -0.48 and -1.38. These results have implications for control of other addictive substances.

Drug and Narcotic Control↗
PubMed2002

A controlled trial of buprenorphine treatment for opium dependence: the first experience from Iran.

AIMS: To evaluate the effect of a 4 mg/day sublingual dose of buprenorphine in the maintenance treatment of opium dependence in comparison with a 1 mg/day dose over an 18-week treatment period. As a secondary objective, the results were determined concurrently for subjects treated with a 2 mg/day dose. DESIGN: Subjects were assigned randomly to three dosage groups. PARTICIPANTS: 330 consecutive (320 men and 10 women) opium addicts who met the DSM-IV criteria for opioid dependence and were seeking treatment. INTERVENTION: Subjects received a 1, 2 or 4 mg/day dose of buprenorphine and were treated in an outpatient clinic where they also received a weekly 1-hour clinical counseling session. MEASUREMENTS: Addiction Severity Index, retention in treatment, and illegal opioid use as determined by random urine testing. FINDINGS: The mean age was 37.5 years (SD=11.4, range 19-72). Overall, 194 (58.8%) of the patients completed the 18 week study. Completion rates by dosage groups were 47.3% for the 1 mg group, 58.2% for the 2 mg group and 70.9% for the 4 mg group (chi(2)=12.7, df=2, P=0.0017). CONCLUSIONS: The results support the efficacy and safety of buprenorphine for opium addiction and suggest that an adequate dose of buprenorphine would help to increase the success rate.

Adult↗
PubMed2004

Twelve-month maintenance treatment of opium-dependent patients.

The goal of this study was to compare the effects of 1, 3 and 8 mg per day doses of buprenorphine in the maintenance treatment of opium-dependent subjects in Iran over a treatment period of 12 months. Participants were randomized to three equal groups (171 subjects per group) of opium-dependent individuals who met the DSM-IV criteria for opioid dependence and were seeking treatment. They were treated in an urban outpatient clinic, offering a 1-hour weekly individual counseling session. Overall, 282 subjects (55%) completed the 12 months study. Completion rates by dosage group were 46 (26.9%) for the 1 mg dose group, 102 (59.6%) for the 3 mg dose group, and 134 (78.4%) for the 8 mg dose group (p =.000). These findings are consistent with previous reports of effective buprenorphine use in western countries as a suitable maintenance treatment for opium dependence.

Adult↗
PubMed1994

Headspace constituents of opium.

The headspace of medicinal opium (Ph. Ned. 8) was analyzed by means of GC-FID, (+EI)-GC-MS (low and high resolution), and GC-FTIR. After olfactoric evaluation of the headspace sample by professional perfumers by the use of the GC-sniffing technique and after correlation tests with trained police dogs, more than 70 components were identified. With regard to the characteristic olfactoric properties of opium only one class of components, namely pyrazines, is of special interest. The synthetic mixture of 2-methyl-, 2,5-, and 2,6-dimethylpyrazine with 2-methoxy-3-isopropyl- and 2-methoxy-3-isobutylpyrazine was found to represent the original opium odour quite well.

Animals↗
PubMed2002

Sphincter of Oddi dysfunction in patients addicted to opium: an unrecognized entity.

BACKGROUND: Opiate-induced sphincter of Oddi dysfunction (SOD) as a clinical entity has not been described. METHODS: Eight chronic opium addicts (all men, mean age 61.3 years, mean duration of addiction 24.75 years) presenting with pancreatobiliary pain and a dilated bile duct with or without dilated pancreatic duct on abdominal US were studied. All patients underwent ERCP and biliary sphincterotomy. In addition, pancreatic sphincterotomy was performed in 4 patients with a dilated pancreatic duct. OBSERVATIONS: At ERCP, the bile duct was dilated in 8 and pancreatic duct in 4 patients. There was delayed drainage of contrast (>45 minutes) from the bile duct in all 7 patients studied, whereas delayed drainage from the pancreatic duct (>9 minutes) was incidentally observed in 3 patients. In 6 patients followed after sphincterotomy for at least 2 years, there was marked relief of symptoms. Transabdominal US at 2 years follow-up revealed a normal bile duct in 5 and persistent albeit minimal dilatation in 1 patient. Acute pancreatitis developed in 4 patients after ERCP and sphincterotomy, which was fatal in one. No patient had any abnormality in the gallbladder on initial or follow-up transabdominal US. CONCLUSION: SOD in opium addicts is a distinct clinical entity, mainly seen in men in this population, that is characterized by a long history of opium addiction and the absence of prior cholecystectomy or associated gallstone disease. Most patients are seen with the classic clinical picture of SOD with marked long-term improvement in symptoms after endoscopic sphincterotomy.

Aged↗
PubMed2006

Urinary excretion of morphine and codeine following the administration of single and multiple doses of opium preparations prescribed in Taiwan as "brown mixture".

Parallel to the "poppy-seed defense" strategy commonly reported in the United States, donors of urine samples tested positive for opiates in Taiwan often claimed the consumption of Brown Mixture (BM) as the source of the observed morphine and codeine. Because BM contains opium powder (10.0-10.5% morphine), opium tincture (0.9-1.1% morphine), or camphorated opium tincture (0.045-0.055% morphine) and is a popular remedy, and heroin use is considered a serious criminal act, the claim of BM use has to be adequately addressed. In this study, BM from seven different manufacturers (5 tablets and 2 solutions) and urine samples from alleged heroin users and volunteers with various ingestion patterns and were analyzed for their morphine and codeine contents. The analytical procedure included hydrolysis, trimethylsilylation, and gas chromatography-mass spectrometry analysis. The contents of morphine and codeine in the tablets were found to be very consistent, but with significant differences in the two BM solutions. Morphine concentrations found in urine specimens collected from volunteers ingesting BM tablets (or solutions) were always < 4000 ng/mL. The following morphine-to-codeine ([M]/[C]) ratios were observed for urine specimens with morphine concentration > or = 300 ng/mL: (A) < 3.0 for volunteers ingesting BM solution and (B) > 3.0 (mostly > 5.0) for volunteers ingesting BM tablets and alleged heroin users. It appeared that (A) BM ingestion (tablet or solution) was unlikely to result in a morphine concentration > 4000 ng/mL; and (B) [M]/[C] ratio might not be an effective parameter to differentiate heroin use from BM tablet ingestion.

Codeine↗
PubMed2003

A tale of three cell types: alkaloid biosynthesis is localized to sieve elements in opium poppy.

Opium poppy produces a diverse array of pharmaceutical alkaloids, including the narcotic analgesics morphine and codeine. The benzylisoquinoline alkaloids of opium poppy accumulate in the cytoplasm, or latex, of specialized laticifers that accompany vascular tissues throughout the plant. However, immunofluorescence labeling using affinity-purified antibodies showed that three key enzymes, (S)-N-methylcoclaurine 3'-hydroxylase (CYP80B1), berberine bridge enzyme (BBE), and codeinone reductase (COR), involved in the biosynthesis of morphine and the related antimicrobial alkaloid sanguinarine, are restricted to the parietal region of sieve elements adjacent or proximal to laticifers. The localization of laticifers was demonstrated using antibodies specific to the major latex protein (MLP), which is characteristic of the cell type. In situ hybridization showed that CYP80B1, BBE, and COR gene transcripts were found in the companion cell paired with each sieve element, whereas MLP transcripts were restricted to laticifers. The biosynthesis and accumulation of alkaloids in opium poppy involves cell types not implicated previously in plant secondary metabolism and dramatically extends the function of sieve elements beyond the transport of solutes and information macromolecules in plants.

Alcohol Oxidoreductases↗
PubMed1989

An epidemic of opium dependence among Asian refugees in Minnesota: characteristics and causes.

After several decades absence, opium smoking has reappeared in the U.S. Introduced by Indochinese refugees in the early 1980's, it has spread to several regions of the country. In this report the characteristics of refugee opium addicts is described. In addition, the factors contributing to a fertile situation for opium addiction are presented. Finally, implications of these findings and remedial recommendations are suggested.

Adult↗
PubMedDate not supplied

Field and laboratory test for raw and prepared opium.

Two new colour tests for opium are described. These may be used alone, as field tests, or in combination with traditional tests rapidly to confirm raw or prepared opium. Absolute confirmation of opium by thin layer chromatography is also useful in the determination of origins. An alternative chromogen to the Dragedorff reagents is described, although iodoplatinate remains the preferred chromogen.

Chromatography, Thin Layer↗
PubMedDate not supplied

[Excretion of catecholamines in development of the opium and alcohol abstinence syndrome and in post-abstinence period].

Excretion of catecholamines has been studied in patients with opium narcotic and alcoholic dependence in developmental dynamics of the opium and alcoholic abstinence syndrome and in the postabstinence period. It has been revealed that 8-10 h after cessation of the psychoactive substances (the preabstinence period) the level of excretion of adrenaline [A], dioxyphenylalanine [DOPA], dopamine [DA] and, to the greatest extent, of noradrenaline [NA] especially in patients with alcoholic dependence decreases in comparison with the control variant. As compared to the control variant the acute form of abstinence syndrome (1-3 days after cessation of the psychoactive substances is characterized by the higher level of the A and DA excretion and the lower level of the NA excretion (especially in patients with opium narcotic dependence). As compared to the preabstinence period under conditions of the acute abstinence syndrome there is an essential increase in the level of the A, NA, DOPA and DA excretion. As compared to the control variant the postabstinence period (10-20 days after cessation) is characterized by the lower level of the NA excretion, especially in patients with alcoholic dependence, and of DOPA. The level of DA decreases in patients with alcoholic dependence. As compared to the acute abstienence syndrome the postabstinence period differs by the lower level of the A, NA (especially in patients with alcoholic dependence), DOPA (only inpatients with alcoholic dependence) and of DA excretion.

Catecholamines↗
PubMed1980

Recovery of thebaine and cryptopine from Indian opium.

The thebaine content of the opium collected in the Madhya Pradesh region of India has been estimated and reported to range from 1.5 to 2.0 per cent. A technological process for the recovery of thebaine from the mother liquor remaining after the separation of natural codeine in the Government Opium and Alkaloid Works, Neemuch, has been developed in the laboratory and stepped up to an industrial scale. A method for the recovery to thebaine from the waste slaked-lime residues obtained from crude alkaloid cake mother liquor in the Government Opium and Alkaloid Works at Ghazipur has been worked out and the technical details of the process described. The recovery of thebaine would help to increase the production of codeine, and thebaine can also be used as a raw material for the manufacture of other drugs. Cryptopine has also been recovered from the mother liquor after the separation of thebaine.

Alkaloids↗
PubMed1994

Opium and infant-sedation in 19th century England.

Infant cordials containing opium were commonly used in Victorian England to quieten babies and young children. The cordials were freely available and sold under a variety of brand names. JANET BRIAN describes the slow progress towards legislative control of the sale of opium and its use in infant cordials, in which opposition from the pharmacy lobby and government reluctance to lose income from the lucrative opium trade played a major part.

Drug Industry↗
PubMed1996

Molecular characterization of berberine bridge enzyme genes from opium poppy.

In Papaver somniferum (opium poppy) and related species, (S)-reticuline serves as a branch-point intermediate in the biosynthesis of numerous isoquinoline alkaloids. The berberine bridge enzyme (BBE) ([S]-reticuline:oxygen oxidoreductase [methylene bridge forming], EC 1.5.3.9) catalyzes the stereospecific conversion of the N-methyl moiety of (S)-reticuline into the berberine bridge carbon of (S)-scoulerine and represents the first committed step in the pathway leading to the antimicrobial alkaloid sanguinarine. Three unique genomic clones (bbe1, bbe2, and bbe3) similar to a BBE cDNA from Eschscholtzia californica (California poppy) were isolated from opium poppy. Two clones (bbe2 and bbe3) contained frame-shift mutations of which bbe2 was identified as a putative, nonexpressed pseudogene by RNA blot hybridization using a gene-specific probe and by the lack of transient expression of a chimeric gene fusion between the bbe2 5' flanking region and a beta-glucuronidase reporter gene. Similarly, bbe1 was shown to be expressed in opium poppy plants and cultured cells. Genomic DNA blot-hybridization data were consistent with a limited number of bbe homologs. RNA blot hybridization showed that bbe genes are expressed in roots and stems of mature plants and in seedlings within 3 d after germination. Rapid and transient BBE mRNA accumulation also occurred after treatment with a fungal elicitor or with methyl jasmonate. However, sanguinarine was found only in roots, seedlings, and fungal elicitor-treated cell cultures.

Amino Acid Sequence↗
PubMed2005

Genetic studies on collar rot resistance in opium poppy (Papaver somniferum L.).

The collar rot disease has been reported recently and occurs at the 10-12-leaf stage of plants of opium poppy. Infected plants topple down and dry prematurely due to fast rotting at the collar region. The inoculum for this study was multiplied on the cornmeal-sand culture. Genetic ratios were calculated by the chi-square test. Inheritance studies on this disease show a monogenic pattern of segregation with the ratio of 3 : 1 at F2, 1 : 2 : 1 at F3 and 1 : 1 at the backcross. Such genetic ratios clearly indicate that a single recessive gene (rs-1) is responsible for disease resistance in opium poppy. The inference drawn on the basis of the present study will be a great help in the future breeding programme of opium poppy for collar rot resistance.

Chromosome Segregation↗
PubMed1976

Experiences of a methadone detoxification programme for opium addicts.

The conduction of a new programme of methadone detoxification of opium addicts in a general hospital setting is described. A blind technique of dispensing methadone in a powdered form mixed with powdered aspirin to two groups of opium addicts was used: Group A were given a gradual reduction of the methadone over a period of ten days, while group B were maintained on the initial stabilising dose for the ten days and then abruptly withdrawn from methadone on the eleventh day. It was observed that the number of complaints and abstinence symptoms was markedly reduced in Group B. It is suggested that this technique is a major improvement over the standard progressive reduction method of methadone detoxification. A follow-up of these patients over a period of 1 1/2 years is reported.

Adult↗