Monday's Molecule #55 was morphine [(5α,6α) -7,8-didehydro-4,5-epoxy- 17-methylmorphinan-3,6-diol]. Morphine is an opiate. It is the main analgesic in opium. Morphine is generally recognized as the strongest pain killer known.Morphine is derived from the creamy latex found in the seed pods of the opium poppy, Papaver somniferum. It seems likely that the opium poppy is derived from wild poppies that grow in the Mediterranean basin. Selection for plants that produce more and more opium has led to the evolution of a new human-made species.
In addition to morphine, the seed pods contain a number of similar opiates; codeine, noscapine, papaverine and thebaine, that are less potent than morphine. It is not clear why wild poppies contain small amounts of these chemicals. Maybe they help prevent the seed pods from being eaten by some animals?
Although opium was widely used in China, it is almost certain that the opium poppy originated in the Middle East and was only imported into China about 400 AD. Historical records suggest that the ancient Sumerians and Egyptians knew about opium and probably used it as a recreational drug.
In addition to its action as a painkiller, morphine produces a sensation of euphoria and well being. Both effects are due to binding of morphine to specific opiate receptors in the brain. Morphine resembles endorphins, which are released in response to stress, and by binding to some opiate receptors further endorphine released is stimulated.The analgesic effect is due to binding to other opiate receptors that block pain transmission at nerve synapses.
See Brandon's Blog: Poison, Medicine, and Things that Grow for some more information on morphine and opiates. The article Toxic Talk (Ed. 8.1) explains the difference between opiates and opioids. Toxic Talk (Ed. 8.0) has a nice description of morphine showing a different view of the structure than the one shown above.
Pure morphine can be converted to codeine by a simple chemical reaction that adds a methyl group to one of the hydroxyl groups on morphine. Codeine is much less effective as a painkiller than morphine and even less effective at inducing euphoria. It has the benefit of being much less addictive (and legal).Heroin was first manufactured by English chemists in the 1870's. Later on it was manufactured and sold by the Bayer pharmaceutical company. Heroin is easily made by boiling morphine solutions (or opium) with acetic anhydride. This produces an acetylated form of morphine that is much more potent than morphine in all its properties . The enhanced effects are probably due to its increased solubility and more efficient transfer to the brain, where heroin is converted back to morphine. Heroin is more addictive than morphine, although susceptibility to opiate addition varies considerably from person to person.
[Image Credti: The rotating three-dimensional image of morphine is from Wikipedia]
One book which I think you would love is:
ReplyDeleteThe Chemistry of Mind-Altering Drugs
And sometime perhaps you could pen a post about how ridiculous the drug laws in this country are. The most ridiculous fact is that cannabis is classified as Schedule 1 substance (most illegal), while THC, the active component, is classified as Schedule 2 (less illegal)
It is not clear why wild poppies contain small amounts of these chemicals. Maybe they help prevent the seed pods from being eaten by some animals?
ReplyDeleteShades of adaptationism, perhaps?
If codeine is so similar to the main "active ingredient", morphine, is it possible that the enzymes that produce morphine also produce small amounts of other, related compounds? My biochemistry knowledge is woefully inadequate.
@ ashutosh:
ReplyDeleteActually, according to this DEA site, marijuana and the various tetrahydrocannibinols (THCs) are all Schedule 1.
Perhaps you're thinking of "dronabinol in sesame oil in soft gelatin capsules" (trade name Marinol), which is a prescription version of THC in a specified dosage form. In that specific form, THC is Schedule 3. In any other form, I believe THC is Schedule 1.
@ Dr. Moran:
In your first paragraph, you describe morphine as the strongest painkiller known, but later describe heroin as more potent than morphine in all respects. (Also, I believe there are other synthetics that are much more potent.)
Did you mean that morphine is the strongest naturally-occurring painkiller?
Endorphins are probably the strongest painkiller, based on amount required to achieve effect.
ReplyDeleteFentanyl and some synthetics are much stronger than morphine. Oxymorphone (not oxycodone) is also one of the strongest, and is the most euphoric.
Morphine is not the strongest pain opioid painkiller. Oxycodone is 1.5 times stronger, for example. Fentanyl family is 100's of times stronger. Morphine is also NOT like endorphins. The latter are small polypeptides, not alkaloids. Both, endorphins (the word means "enodgenous morphine" although chemically they have nothing to do with each other. It's just an accident of nature that they bind to the same receptors).
ReplyDeleteThusly, both endorphins & opioids bind to G-protein coupled mu1, mu2, delta, sigma, kappa, ORL1, etc receptors thusly blocking pain, producing euphoria, constipation, etc. depending on where in the body they bind (e.g. nucleus accumbens, GI tract, immune cells, etc).
If you take opioids for longer than 3 weeks, you will cause downregulation of your natural endorphin receptors as well as decrease in endorphin syntehsis. This brings physical dependence and tolerance. Your first withdrawals will rock your world in a bad way, but they will be mild compared to what is in store for you if you continue down this path.
Because external opioids affect the risk-reward circuits in nucleus accumbens, if you start taking them while your brain is still developing (e.g. as a teenager), will cause permanent brain changes and you will likely need them for the rest of your life.
So, don't start and if you are just starting, quit while you are still ahead.
HI, does anyone konw a person like goethe, Einstein, Darwin etc, who did not use drugs?
ReplyDeleteBe sure, each SCIENTIST needs it!
greetings from neinstein