From: (N. Pound) Subject: Re: Heroin vs. opium? Date: 1996/12/10 newsgroups: alt.drugs.hard >There certainly *is* a rush with morphine, what makes you think that the >superior rush makes heroin a lot more addictive? Clinically there are some important differences between the two analgesics. Heroin is more likely to produce euphoria and addiction than morphine, but tends to cause less nausea, constipation and hypotension. Most importantly, the analgesic potency of diamorphine and its greater solubility allows effective doses to be injected in smaller volumes of fluid. >The main difference between them is that heroin passes the blood/brain >barrier more easily than morphine due to its chemical structure, and it >is about 4 times stronger weight for weight. Apart from those 2 >differences, there is no other substantive difference due to the fact >that heroin de-acetylizes back to morphine hydrochloride quite rapidly >once inside the body. What????? How can heroin be 4 times stronger than morphine, and be no different to morphine since it is converted back to morphine once inside the body????? If all the actions of heroin were mediated by its conversion back to morphine then weight for weight it would be less potent since in its un-metabolised form it has all those extra, useless acetyl groups stuck onto it adding dead weight!!!! Heroin (3,6-diacetylmorphine) does have two active metabolites: 6-acetylmorphine and morphine. However, it does act as an agonist at opioid receptors itself so not all of its effects can be accounted for by references to its metabolites. Heroin differs from morphine in its affinity to the various types of opioid receptor. Since receptor populations vary across different areas of the body heroin will thus exhibit a different pattern of physiological effects to morphine. E.g. heroin has less affinity for the receptors in the guts which regulate motility and thus tends to produce less constipation. If heroin was simply a more potent version of morphine we should expect more constipation, not less. Bottom line, heroin is qualitatively different to morphine. In clinical terms it tends to produce more euphoria, and euphoria which is qualitatively different from that produced my morphine at high doses. That's why people prefer to take the stuff given the choice. It's also why US physicians are so afraid to prescribe the stuff to patients (completely unjustified IMHO, witholding effective pain relief). Nick P. ==================================================================== From: (N. Pound) Subject: Morphine vs Heroin (was: Heroin vs. opium?) Date: 1996/12/13 newsgroups: alt.drugs.hard >> Therefore, diamorphine must be having some actions in its own right >> otherwise it couldn't be a more potent analgesic, weight for weight. >Nick (Canada, not England), I think i see what your driving at. People >should understand that this is an "academic" challenge, though, and that >it is not in dispute that _most_ of heroin's effect is exerted by the >morphine and (possibly) 6-mam to which it is metabolized. (Y'all don't get >too confused). Samson is right about this, and I do not dispute that _most_ of heroin's effects are mediated by its conversion to morphine. I think the real question is; what makes heroin different? Is it that it is merely an extremely efficient system for delivering morphine to just the right places to produce analgesia and euphoria? Or does it have actions in its own right? Actions which distinguish it from morphine? Well before I tackle this issue theres something we should be able to agree upon. And this is important because people with better (or worse) things to to with their time might not read on..... Whether or not the analgesic effects of heroin are entirely mediated by its conversion to morphine there are important clinical differences between the drugs. Heroin has certain advantages over morphine for palliative care. 1. It is more soluble so effective doses can be injected in smaller volumes of fluid. This is especially important when the patient is emaciated and yet needs large doses. 2. It causes less constipation, nausea & hypotension than morphine. Now whatever the reasons for these differences the advantages are extremely important clinically. Larger doses of morphine are no substitute. Now lets get down to the dispute over the physiological basis for these differences. I don't think we're going to find a clear answer though. There are important species differences to consider. In many strains of mice both morphine and heroin act on mu-opioid receptors in the brain to produce analgesia.However, in the Swiss Webster strain heroin exhibits selectivity for delta receptors, whereas morphine still acts at the mu-site. In these mice, not only does heroin act at delta receptors in the brain, but so does its metabolite 6-monoacetylmorphine (MAM). Furthermore, heroin exhibits selectivity for the delta-1 subtype of opioid receptor, whereas MAM acts primarily at the delta-2 sub-type. Clinically these findings are important because certain types of analgesia in these mice depend critically on the activation of the delta receptors. For more information on this see: Rady, et al. (1994). J.Pharm.Exp.Ther., 268(3):1222-31. Rady, et al. (1994). Life Sciences, 55(8):603-9. >......... without need of postulating a diamorphine receptor. As >far as _I_ know, no such beast has been found. (I'm sure it has some >action at mu sites, but as i understand, it is almost negligible. Then >again, you may -- and probably do -- know something i don't). Well, to tell the truth I didn't know of heroin's selectivity for delta-1 receptors in these mice until your posting prompted me to do some hunting. Anyway, I don't think that these receptors would ever deserve to be called "heroin receptors". There are probably other, far more specific ligands. What it all means for us naked apes is difficult to say. If our species has types of opiate receptors that exhibit selectivity for heroin then that would fit with what I've been arguing. If not then I'd have to go with Samson's "lubricated morphine" theory. I don't think we can be definitive on this point at present. >Perhaps it is, rather, that 6-mam is more potent than morphine? This may indeed be the case, in some places. If so then it's another good reason for considering heroin to be a rather different drug to morphine. You don't get the MAM without the H. If it's the MAM that's most important then morphine alone would be no substitute for heroin. This incidently allows for drug testing which can discriminate between heroin and morphine use. If there's 6-monoacetylmorphine in the urine then heroin must be involved. Nick P.