DiHydroEtorphine Anyone?

Fentasies · Mon Jul 11, 2005 5:40 am

Ive yet to see any discussion of DHE. This being for the opi fans such as myself.

Has anyone here researched it any bit and care to add anything? It sounds promising as you will see below,

In Future Synthetic Drugs of Abuse it states (in regards to Etorphine);
In any discussion of synthetic analgesics one must include the so called Bentley compounds. These compounds are not, in the purest sense, synthetic analgesics as they are C-ring etheno Diels Alder adducts of thebaine12. Etorphine (compound 47, Figure 14) is perhaps the best known compound in the series and has analgesic activity approximately 1000 times that of morphine13,71. Although reaction conditions appear to be critical, the synthesis of etorphine derivatives involves what is essentially a two step reaction with methylvinylketone and an appropriate organometallic reagent49,64. Hence, the only expected difficulty in the clandestine synthesis of these compounds would lie in the initial acquisition of the thebaine. Therefore, it is somewhat surprising that either etorphine or derivatives thereof have not become a contributor to illicit analgesic supplies. On the other hand, if etorphine were to be admixed with some less potent analgesic, such as heroin, it is doubtful that it would ever be detected.

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Potent reinforcing effects
of dihydroetorphine in rats
by
Greenwald MK, June HL, Stitzer ML, Marco AP
Department of Psychiatry and Behavioral Sciences,
Johns Hopkins University School of Medicine,
Baltimore, Maryland, USA.
J Pharmacol Exp Ther 1996 Jun; 277(3):1228-36
ABSTRACT

Dihydroetorphine is a novel opioid that is an extremely potent analgesic in rodents. The reinforcing potency was determined in rats trained to self-administer heroin and compared to those of fentanyl, heroin, 6-acetylmorphine and morphine for assessment of the abuse potential of dihydroetorphine using a procedure that determines the dose-effect curve in individual sessions. Dihydroetorphine produced a bimodal dose-effect curve similar to that of other opioids. Potency ratios were determined with morphine for the ascending and descending limbs of the dose-effect curve, as well as the dose that yielded maximal response rate. Fentanyl, heroin and 6-acetylmorphine were approximately 100, 8 and 2 times more potent than morphine in maintaining self-administration, respectively. Dihydroetorphine was roughly 1500 to 3000 times more potent than morphine, however, depending upon the limb of the dose-effect curve used for comparison. These potency ratios of dihydroetorphine to morphine were somewhat less than has been reported for analgesia assays, and therefore this compound may have some clinical advantages over other opioids. However, these studies indicate significant abuse liability for dihydroetorphine given its potency in maintaining self-administration in these animals.

Im surprised to see no mention of DHE or Etorphine on Rhodiums archives, perhaps I missed it, but did not see it. Regarding pharmacology, it appears to be a heavy opioid mu receptor agonist as far as ive seen. Below is a few peices of info;

Agonist and antagonist properties of dihydroetorphine for mu-opioid receptors in mice.
Kamei J, Suzuki T, Nagase H.
Department of Pathophysiology and Therapeutics, Faculty of Pharmaceutical Sciences, Hoshi University, Tokyo, Japan.
To test the hypothesis that dihydroetorphine has opioid antagonist properties, we examined the effects of dihydroetorphine on the antinociceptive effect of morphine. The antinociceptive response was evaluated by recording the latency in the tail-flick test using radiant heat as a stimulus. The antinociceptive effect of dihydroetorphine reached its peak 30 min after administration, and remained significant up to 90 min after administration. On the other hand, when dihydroetorphine was injected i.c.v., the antinociceptive effect of dihydroetorphine reached its peak 15 min after administration, and a significant antinociceptive effect disappeared within 90 min after administration. When morphine was administered 30 min after dihydroetorphine, the antinociceptive effect of morphine was significantly enhanced. In contrast, the antinociceptive effect of morphine was significantly reduced when morphine was administered 120 min after either i.p. or i.c.v. administration of dihydroetorphine. This antagonistic effect remained significant up to 6 h after administration of dihydroetorphine, and then gradually decreased. However, dihydroetorphine had no significant effect on the antinociceptive effect of either trans-(+/-)-3,4-dichloro-N-methyl-N-(2(1-pyrrolidinyl) cyclohexyl)-benzeneacetamide (U-50, 488H), a kappa-opioid receptor agonist, or [D-Pen2.5]enkephalin (DPDPE), a delta-opioid receptor agonist. These results suggest that dihydroetorphine may have a reversible antagonist effect for mu-opioid receptors, but not for kappa- or delta-opioid receptors, when its agonistic activity disappears.

For more see;
http://jpet.aspetjournals.org/cgi/content/full/296/2/528

It seems in my understanding of opioid pharmacology, youd wish to keep kappa activity minimal, as it can be major factor in severe respiratory depression, and have high mu-1 receptor activity, from a dealers point of view, as this leads to greater euphoria and apparently addiction. Combined with a lower activity life, you present a more fiendish compound, like crack cocaine, the shorter it lasts the more the user fiends, regardless of euphoria. This may be a primative way to put it, but logically it makes sense.

Another interesting note and hint to the future;
( taken from http://www.deadiversion.usdoj.gov/fed_regs/rules/2000/fr1117.htm )
Dihydroetorphine is the international non-proprietary name for a chemical substance which is chemically similarto etorphine. It is an opiate-like substance that is 3-4 order of magnitude (1000 to 10,000 times) more potent than morphine but with a shorter duration of action. The effects of dihydroetorphine and its psychological dependence liability are similar to those produced by heroin. Animal studies demonstrate that it is a highly potent analgesic with effects that begin within 15 minutes of administration and the effects last from 60-90 minutes. Dihydroetorphine was registered in China in December of 1992 for the relief of acute severe pain. However, abuse of dihydroetorphine began soon after it was marketed in China in 1992. Dihydroetorphine is not marketed or used medically in the United States. As a thebaine derivative, dihydroetorphine is controlled in Schedule II of the CSA in the United States.

As is bolded above, its abuse potential has already been seen in humans, however it never made it into the mainstream drug markets (USA/europe), and therefore its 'true' abuse has never been shown, yet. Shall we change that? Smile

Pastor John Hagee · Mon Jul 11, 2005 6:40 am