When administered intra-peritoneally in rats, morphine-6-sulfate exhibits much greater analgesic effect than morphine 134, suggesting that it may possess pharmacological activity similar to M6G. However, the contribution of morphine-6-sulfate to the effects of heroin must be negligible, as negligible are the plasma concentrations of this metabolite after administration of morphine or heroin in humans 67. PM usually suffer more adverse reactions at a normal dose of drug, due to being homozygous for either functionally variant alleles or due to a complete deletion of the gene causing reduced enzyme activity 56. UM with two or more active genes on the same allele often fail to respond to drugs at a normal dose 44. Therefore, genetic polymorphisms in CYP genes may play important roles in the optimization of drug treatments with respect to efficacy and prediction of adverse reactions 48.
Metabolism of cocaine and heroin is catalyzed by the same human liver carboxylesterases
However, the striatal Cmax of 6-MAM after heroin administration in the rat is about 50% higher than after equimolar doses of 6-MAM 31, indicating that, at least in the rat, a significant fraction of brain 6-MAM results from the local deacetylation of heroin. Finally, we have emphasized the role of dopamine-independent mechanisms in heroin reward, without discounting the possible contribution of dopamine-dependent mechanisms, particularly in the case of 6-MAM. In this respect it is important to notice that major differences in the ability to engage dopaminergic transmission are not limited to heroin and its metabolites. Even more dramatic differences are evident when opiates like morphine are compared to synthetic opioids, such as oxycodone 263.
Associated Data
The chemical structures of morphine and its metabolites are closely related to the clinical effects of drugs (analgesia and side-effects) and to their capability to cross the Blood Brain Barrier (BBB). Morphine-6-glucuronide (M6G) and Morphine-3-glucuronide (M3G) are both highly hydrophilic, but only M6G can penetrate the BBB; accordingly, M6G is considered a more attractive analgesic than the parent drug and the M3G. In this review we will discuss recent advances in the field, considering brain disposition of M6G, UDP-glucoronosyltransferases (UGT) involved in morphine metabolism, UGT interindividual variability and transport proteins. The substances that result from metabolism (metabolites) may be inactive, or they may be similar to or different from the original drug in therapeutic activity or toxicity. Some drugs, called prodrugs, are administered in an inactive form, which is metabolized into an active form. Metabolites may be metabolized further instead of being excreted from the body.
- At this point in time, the brain ECF 6-MAM concentration was already of the same order of magnitude and continued to rise thereafter, reaching the Cmax 4.3 min after the heroin injection when almost no heroin was found in the brain ECF.
- The induction and inhibition of CYPs, which can mediate DDI and the bioactivation of xenobiotics is profound and clinically important 111.
- Bolus model was used, whereas an extravascular model was used for the metabolites in blood and all the compounds in brain ECF.
- In contrast, it has been shown that heroin efficacy, as indicated by MOP-mediated G-protein activation, is higher than that of morphine and M6G, and at least comparable to that of 6-MAM 86.
- As people age, enzymatic activity decreases, so that older people, like newborns, cannot metabolize drugs as well as younger adults and children do (see Aging and Drugs).
How Does the Heroin Chemical Formula Impact Metabolism?
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- This is one of several substances that heroin can be broken down into when metabolized in the body.
- Health care professionals need to be especially cautious when dealing with patients with diminished metabolic capacities due to organ dysfunction.
- However, caution should be applied in extending data collected in rodents to humans, given the much faster metabolism of heroin in mice and rats relative to humans (compare Figs. Figs.22–4).
- The rate at which heroin exits the body affects how long it will take before the substance is no longer detectable in various drug tests.
Heroin administration, morphine concentrations peak at 10–12.6 min in the blood and at 24 min in the striatum (supplementary material in 31) and then decline very slowly (see Fig. 5). Heroin is a highly potent opioid, and its effect can last longer than some other illicit substances such as meth or cocaine, but the question is, how long does heroin stay in your system? If it takes only about 30 minutes for the half-life of heroin to break down into metabolites, then how is this substance detected days later? Heroin metabolism in the system in reference to body fluids can take 5-6 hours. This is regardless of heroin half-life, with the exception of other parts such as hair follicle and urine; hence this process varies from one individual to the other.
Heroin and its metabolites: relevance to heroin use disorder
- Administration of heroin in the rat 20 and transfer rate constants were estimated after subcutaneous administration in the mouse 21.
- In this case, they are merely delivery devices – sort of molecular UPS trucks.
- However, in the already mentioned study by Martin and Fraser 181, when equianalgesic doses of heroin and morphine were administered double-blind to opiate-experienced users, no difference in desirable effects (including euphoria, relaxation, and ‘drive’) was reported.
- Morphine clearance and accumulation of its M3G metabolite are increased in cirrhosis, making dose adjustments advisable.
This guide provides all the information on how heroin, after ingestion through a specific route, degrades into other detectable substances. how long does heroin stay in your system The half-life of heroin is 30 minutes; this may vary due to certain factors such as genetics, physical characteristics, amount, and composition of the substance. These variables contribute largely to the complete degradation and production of detectable secondary metabolites in the body. With respect to heroin 171, 6-MAM is nearly equipotent in inducing naloxone-reversible psychomotor activity 172–174 and psychomotor sensitization following repeated administration 175.
Administration, we gave a bolus injection of heroin to rats and measured the concentration of heroin and its metabolites in blood and brain extracellular fluid (ECF). Administration 25, 47, 147, consistent with the literature that questions the contribution of dopamine transmission to heroin reward 222–225. A great deal of research has investigated the reinforcing effects of heroin and morphine using i.v. These studies have shown greater reinforcing potency of heroin relative to morphine 212, 213. This is consistent with the slower onset of action of morphine relative to heroin 72, 73, 214 and matches the anecdotal preference for heroin over morphine reported by opioid users 215. More pronounced adverse effects for morphine vs. heroin 216 or for heroin vs. morphine 217 were reported.
