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Disposition and Metabolism of Drugs of Dependence
Published in S.J. Mulé, Henry Brill, Chemical and Biological Aspects of Drug Dependence, 2019
Following intrapoplital injection of 75 mg/kg in the rat, the peak level of drug (0.9 Mg/g) was attained in brain 15 minutes after injection which declined to barely detectable levels in 60 minutes. The peak level of its deacetylation product, 6-monoacetylmorphine in brain was 6.3 μg/g 15 minutes after injection, which declined to 1.9 μg/g at 2 hour period. The peak levels of morphine derived from heroin (1.8 μg/g) were, however, sustained for about 2 hours. In mouse, following an intravenous injection of 37.5 mg/kg, the levels of heroin, 6-monoacetylmorphine and morphine in brain at 2.5 minutes were 8.2, 23, and less than 2 μg/g, respectively. At 7.5 minutes heroin was barely detectable in brain, but morphine concentrations reached a peak (5 μg/g) at 15 to 30 minutes after injection and a drop in level of 6-monoacetylmorphine to morphine levels was also noticed during this time. It was concluded that the pharmacologic effects of heroin are mediated primarily by 6-monoacetylmorphine and morphine.53,162
Evaluation of substance use in Izmir during the COVID-19 pandemic
Published in Journal of Substance Use, 2022
Melike Aydoğdu, Rukiye Aslan, Özge Can, Yusuf Ali Altunci, Serap Annette Akgür
Amphetamine-type stimulants (ATS) (amphetamine, methamphetamine, and 3,4-methylenedioxymethamphetamine(MDMA)), benzodiazepine, buprenorphine, cannabis (THC-COOH), cocaine (benzoylecgonine), opiates (morphine, codeine, and 6-monoacetylmorphine (6-MAM)), and their metabolites in urine samples were analyzed in the Addiction Toxicology Laboratory (Republic of Turkey Ministry of Health, 2016). All samples were collected under supervision, and the urine temperature was measured. Urine integrity test (Intect 7 strip test containing creatinine, pH, density, bleach, nitrite, glutaraldehyde, and pyridinium chlorochromate) was applied to each urine sample that reached the laboratory within the scope of safety and custody chain. Screening analyses were carried out by enzymatic immunoassay methods: cloned enzyme donor immunoassay (CEDIA) and Diagnostic Reagents Inc (DRI) (Themo) in 2017 and 2018 and using biochip technology (Randox) in 2020. Cutoff values of parameters used for screening analysis were given in Table 1. Results over these values were considered positive, while results below these values were considered negative. Samples with positive screening test results were confirmed by Liquid Chromatography-Mass Spectrometry (LC-MS) method (Bruker Corporation, USA) and Gas Chromatography-Mass Spectrometry (GC-MS) (Thermo Scientific). Results with more than two positives were grouped as multiple items.
Is it possible to design a clinically viable heroin vaccine? The progress and pitfalls
Published in Expert Opinion on Drug Discovery, 2022
Therese J. Ziaks, Candy S. Hwang
Significant advances have been made in preclinical heroin vaccine development, involving multiple iterations of haptens, carrier proteins, and adjuvants. These studies have conducted testing in both sexes of mice, rats, and monkeys on a manifold of characterization and behavioral experiments including: antibody titers, binding, concentration, antinociception, self-administration, lethality, blood-brain distribution, and drug discrimination [1,8,9,12]. Comprehensive reviews assessing vaccine effectiveness and preclinical behavioral metrics are available [8,9]. One challenge unique to heroin (relative to other opioids) is that heroin rapidly metabolizes to 6-monoacetylmorphine (6-AM (5)), the primary mediator of heroin reinforcement, which is then further metabolized to morphine (6, Figure 1(a)). To address this issue, researchers designed a ‘dynamic’ heroin hapten (8, Figure 2) [13][1,12], which stimulates antibodies for all three psychoactive metabolites. Other approaches include modifying the hydrolysable acetyl groups of 1 with amides (10) [14,15] or sulfonates (9) [16] to closely mimic 1 or 5 directly, or use a morphine-based hapten (11) to mimic 6 (Figure 2) [17,18]. These haptens can be further differentiated by conjugation method and linker attachment
Fentanyl and other opioid involvement in methamphetamine-related deaths
Published in The American Journal of Drug and Alcohol Abuse, 2022
Zheng Dai, Marie A. Abate, Caroline P. Groth, Tori Rucker, James C. Kraner, Allen R. Mock, Gordon S. Smith
Patterns of methamphetamine-related deaths from 2013 to 2018 were examined in six mutually exclusive subgroups in a hierarchical approach: 1) Methamphetamine only, 2) Methamphetamine + fentanyl/FAs excluding heroin, defined as any presence of fentanyl or a FA, excluding heroin but including any other substances, 3), Methamphetamine + fentanyl/FAs + heroin, defined as concomitant presence of fentanyl/FAs and heroin, plus any other substances, 4) Methamphetamine + heroin, excluding fentanyl/FAs but including any other substances, 5) Methamphetamine + prescription opioids (e.g., oxycodone, hydrocodone, methadone, morphine, etc.) excluding fentanyl/FAs or heroin, and 6) Methamphetamine + any non-opioid substances, e.g., ethanol, marijuana, benzodiazepines. Heroin presence was verified by identification of 6-monoacetylmorphine or heroin in any sample tested (e.g., urine, blood). Descriptive statistics also characterized the methamphetamine-related deaths and the National Center for Health Statistics’ urban-rural classification scheme determined county rurality (13). Peripheral blood concentrations (femoral or subclavian) were used for toxicological analyses of the primary drugs studied, methamphetamine and fentanyl. In addition, methamphetamine concentrations were analyzed both in the presence and absence of fentanyl. Heroin was considered present when the drug or its metabolite 6-monoacetylmorphine (6-MAM) were identified in any sample (e.g., blood, urine, vitreous fluid) tested, with the femoral or subclavian blood concentration ratio of morphine to codeine also considered when heroin involvement was suspected. Since 6-MAM is metabolized fairly rapidly to morphine, morphine concentrations were reported here.