6-o-monoacetylmorphine and Pain

The interpretation of toxicological findings is critical for the thorough investigation of the use and abuse of psychoactive substances. A positive analytical result for a sample taken could usually result in criminal proceedings and a punitive outcome for the defendant whose sample was analysed. The detection of markers of illicit opiate misuse is important both in the management of substance misuse and in the postmortem identification of illicit opiate use. The aim of this study was to emphasise the role of opiate biomarkers available at the laboratory and in the clinical environment. Urine remains the biological tool of choice for qualitative detection of illicit drug use in a clinical setting, while quantitative accuracy remains strictly the domain of blood. Accurate interpretation of the screening tests within a clinical setting alongside other relevant information remains the key to the usefulness of any test. Moreover, the finding of a morphine/codeine concentration ratio in blood exceeding unity is a strong evidence that the person had used heroin, as opposed to having taken a prescription analgesic drug containing codeine.

Topics: Biomarkers; Humans; Morphine Dependence; Morphine Derivatives; Opiate Alkaloids; Opioid-Related Disorders; Pain; Substance Abuse Detection

Heroin is currently being advocated by some as a superior therapeutic agent for use in terminal illness. However, a review of the literature on heroin presently available does not support this contention. Administered orally, heroin is approximately 1.5 times more potent than morphine in controlling chronic pain in terminal cancer patients. Its effects on mood and the incidence and nature of side effects do not differ from those of morphine except in males where poorer pain control probably accounts for the worse effect on mood. Given parenterally for acute pain, heroin is 2-4 times more potent than morphine and faster in onset of action. When the potency difference is accounted for, the pharmacological effects of heroin do not differ appreciably from those of morphine. Heroin is metabolized to 6-acetylmorphine and morphine. After oral administration of heroin, morphine but not heroin or 6-acetylmorphine is detected in blood. In this case, heroin is a prodrug for the delivery of systemic morphine. Following acute i.v. administration, heroin appears transiently in blood with a half-life of about 3 min. The half-life of heroin exposed to blood or serum in vitro is 9-22 min, indicating that organ metabolism is involved in blood clearance as well. Direct renal clearance of heroin is less than 1% of the administered dose. In animal studies, heroin and 6-acetylmorphine are both more potent and faster acting than morphine as analgesics, effects attributed to their greater lipid solubility and subsequent penetration of the blood-brain barrier. Given centrally, morphine is more potent than heroin and 6-acetylmorphine in producing analgesia.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Analgesia; Animals; Brain; Codeine; Depression; Euphoria; Female; Half-Life; Heroin; Humans; Hydromorphone; Kinetics; Liver; Male; Morphine; Morphine Derivatives; Neoplasms; Pain; Sex Factors; Solubility; Terminal Care; Water

Liquid chromatography tandem mass spectrometry was used to identify and confirm the presence of 6-acetylmorphine and morphine in 22,361 urines of pain management patients. Thirty urines tested positive for 6-acetylmorphine above a cutoff of 10 ng/mL. Twenty-three percent of the patients with urinary concentrations of 6-acetylmorphine above 10 ng/mL had urinary morphine concentrations below 300 ng/mL.

Topics: Analgesics, Opioid; Analytic Sample Preparation Methods; Chromatography, High Pressure Liquid; Glucuronidase; Humans; Hydrolysis; Morphine; Morphine Derivatives; Pain; Reference Values; Spectrometry, Mass, Electrospray Ionization; Substance Abuse Detection; Tandem Mass Spectrometry; United States

CD-1 mice were treated intravenously with streptozotocin, 200 mg/kg, and tested 2 weeks later or treated with 60 mg/kg and tested 3 days later. Both treatments changed the tail flick response of heroin and 6-monoacetylmorphine (6 MAM) given intracerebroventricularly from a mu- to delta-opioid receptor-mediated action as determined by differential effects of opioid receptor antagonists. The response to morphine remained mu. Heroin and 6 MAM responses involved delta1 (inhibited by 7-benzylidenenaltrexone) and delta2 (inhibited by naltriben) receptors, respectively. These delta-agonist actions did not synergize with the mu-agonist action of morphine in the diabetic mice. The expected synergism between the delta agonist, [D-Pen2-D-Pen5]enkephalin (DPDPE), and morphine was not obtained in diabetic mice. Thus, diabetes disrupted the purported mu/delta-coupled response. In nondiabetic CD-1 mice, heroin and 6 MAM produced a different mu-receptor response (not inhibited by naloxonazine) from that of morphine (inhibited by naloxonazine). Also, these mu actions, unlike that of morphine, did not synergize with DPDPE. The unique receptor actions and changes produced by streptozotocin suggest that extrinsic in addition to genetic factors influence the opioid receptor selectivity of heroin and 6 MAM.

Topics: Analgesics, Opioid; Animals; Anti-Bacterial Agents; Benzylidene Compounds; Diabetes Mellitus, Experimental; Dose-Response Relationship, Drug; Drug Interactions; Enkephalin, D-Penicillamine (2,5)-; Enkephalins; Heroin; Injections, Intraventricular; Male; Mice; Morphine; Morphine Derivatives; Naloxone; Naltrexone; Narcotic Antagonists; Nociceptors; Pain; Receptors, Opioid, delta; Receptors, Opioid, mu; Streptozocin; Time Factors

The purpose of this study was to determine which delta (delta) opioid receptor subtype, delta 1 or delta 2, was involved in producing the antinociceptive action of heroin and 6-monacetylmorphine (MAM) in Swiss Webster mice. Previous work from this laboratory established that heroin and MAM, given intracerebroventricularly (i.c.v.) in Swiss Webster mice, produce antinociception through activation of supraspinal delta receptors. Naltrindole, but not naloxone or nor-binaltorphimine, antagonizes the inhibitory action of heroin and MAM in the tail-flick test. Recent literature documents the occurrence of subtypes of the delta opioid receptor and the availability of selective antagonists. 7-Benzylidenenaltrexone (BNTX) antagonizes the antinociception induced by delta 1 receptor agonists without affecting that induced by delta 2 receptor agonists. Naltriben (NTB) selectively inhibits delta 2- but not delta 1-induced antinociception. In the present study BNTX and NTB were administered i.c.v. with heroin and MAM to determine the delta receptor subtype responsible for inhibition of the tail-flick response in Swiss Webster mice. The ED50 for heroin-induced antinociception was increased 19-fold by BNTX and was not altered by NTB administration. On the other hand, the ED50 value of MAM was increased 3-fold by NTB and was not altered by BNTX administration. These results suggest that heroin activated supraspinal delta 1 receptors and MAM acted on supraspinal delta 2 receptors to produce antinociception in Swiss Webster mice.

Topics: Animals; Benzylidene Compounds; Heroin; Male; Mice; Morphine Derivatives; Naltrexone; Pain; Receptors, Opioid, delta

We measured blood concentrations of heroin and its active metabolites, 6-acetylmorphine and morphine, serially in 11 patients with chronic pain (9 of whom had cancer) after intravenous injection, intravenous infusion, intramuscular injection, and an oral dose of heroin hydrochloride. Parenteral heroin provided measureable blood levels of heroin, 6-acetylmorphine, and morphine. Blood levels of heroin and 6-acetylmorphine reached their maximal concentrations within minutes and were cleared rapidly. The mean half-life of heroin (+/- S.D.) after intravenous injection or infusion was only 3.0 +/- 1.3 minutes, and the mean clearance of heroin from the blood at apparent steady state was 30.8 +/- 2.1 ml per kilogram of body weight per minute. Morphine levels rose more gradually, and morphine was cleared much more slowly. Oral administration of heroin resulted in measurable blood levels of morphine but not of heroin or 6-acetylmorphine. The amount of circulating morphine provided by an oral dose of heroin was only 79 per cent of that available from an equal amount of morphine. We conclude that heroin is a pro-drug that serves to determine the distribution of its active metabolites. Parenteral heroin is rapidly converted to 6-acetylmorphine, which contributes to rapid pain relief. Oral heroin is converted to morphine and appears to be an inefficient means of providing morphine to the systemic circulation.

Topics: Administration, Oral; Adult; Aged; Biological Availability; Chronic Disease; Female; Half-Life; Heroin; Humans; Infusions, Parenteral; Injections, Intramuscular; Injections, Intravenous; Kinetics; Male; Middle Aged; Morphine; Morphine Derivatives; Pain; Pain, Intractable; Time Factors