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Foxglove
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Why is Tramadol in the same group as Opiates if its not one?
      #208223 - 12/16/04 04:23 PM



Please help clarify this, is it because of the possible dependency and heavy withdraw potential, that it is classified as one of these. I thought that Tramadol was just a super-Ultram?

Thanks

Live life long enough to enjoy it!

--------------------
The goal of life is living in agreement with nature.
-Zeno, greek Philosopher(335-263B.C.)


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armywife
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Re: Why is Tramadol in the same group as Opiates if its not one? [Re: Foxglove]
      #208224 - 12/16/04 04:27 PM

Tramadol is the generic Ultram. I know others here can answer this on ebetter than I can, but basically tramadol acts very much like an opiate, even though it is not one. That is my understanding. If I am wrong please correct me.

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seaofyouth
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Re: Why is Tramadol in the same group as Opiates if its not one? [Re: Foxglove]
      #208225 - 12/16/04 04:35 PM

Quote from Opioids.com

"(+/-)-Tramadol is a synthetic analogue of codeine. It is a central analgesic with a low affinity for opioid receptors. Its selectivity for mu receptors has recently been demonstrated, and the M1 metabolite of tramadol, produced by liver O-demethylation, shows a higher affinity for opioid receptors than the parent drug. The rate of production of this M1 derivative (O-demethyl tramadol), is influenced by a polymorphic isoenzyme of the debrisoquine-type, cytochrome P450 2D6 (CYP2D6). Nevertheless, this affinity for mu receptors of the CNS remains low, being 6000 times lower than that of morphine. Moreover, and in contrast to other opioids, the analgesic action of tramadol is only partially inhibited by the opioid antagonist naloxone, which suggests the existence of another mechanism of action. This was demonstrated by the discovery of a monoaminergic activity that inhibits noradrenaline (norepinephrine) and serotonin (5-hydroxytryptamine; 5-HT) reuptake, making a significant contribution to the analgesic action by blocking nociceptive impulses at the spinal level. (+/-)-Tramadol is a racemic mixture of 2 enantiomers, each one displaying differing affinities for various receptors. (+/-)-Tramadol is a selective agonist of mu receptors and preferentially inhibits serotonin reuptake, whereas (-)-tramadol mainly inhibits noradrenaline reuptake. The action of these 2 enantiomers is both complementary and synergistic and results in the analgesic effect of (+/-)-tramadol. After oral administration, tramadol demonstrates 68% bioavailability, with peak serum concentrations reached within 2 hours. The elimination kinetics can be described as 2-compartmental, with a half-life of 5.1 hours for tramadol and 9 hours for the M1 derivative after a single oral dose of 100mg. This explains the approximately 2-fold accumulation of the parent drug and its M1 derivative that is observed during multiple dose treatment with tramadol. The recommended daily dose of tramadol is between 50 and 100mg every 4 to 6 hours, with a maximum dose of 400 mg/day; the duration of the analgesic effect after a single oral dose of tramadol 100mg is about 6 hours. Adverse effects, and nausea in particular, are dose-dependent and therefore considerably more likely to appear if the loading dose is high. The reduction of this dose during the first days of treatment is an important factor in improving tolerability. Other adverse effects are generally similar to those of opioids, although they are usually less severe, and can include respiratory depression, dysphoria and constipation. Tramadol can be administered concomitantly with other analgesics, particularly those with peripheral action, while drugs that depress CNS function may enhance the sedative effect of tramadol. Tramadol should not be administered to patients receiving monoamine oxidase inhibitors, and administration with tricyclic antidepressant drugs should also be avoided. Tramadol has pharmacodynamic and pharmacokinetic properties that are highly unlikely to lead to dependence. This was confirmed by various controlled studies and postmarketing surveillance studies, which reported an extremely small number of patients developing tolerance or instances of tramadol abuse. Tramadol is a central acting analgesic which has been shown to be effective and well tolerated, and likely to be of value for treating several pain conditions (step II of the World Health Organization ladder) where treatment with strong opioids is not required.


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piper65111
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Re: Why is Tramadol in the same group as Opiates if its not one? [Re: seaofyouth]
      #208227 - 12/16/04 04:38 PM

It is extremly addicting I used to be addicted to it .Not fun.AQnyone else have a problem with it.

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AngelWolf13
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Re: Why is Tramadol in the same group as Opiates if its not one? [Re: piper65111]
      #208481 - 12/17/04 02:15 PM

ultram did absolutely NOTHING for me except for give me a headache. they are really not a narcotic and i have no idea why they are grouped with opiates. they are way more readily prescribed than any true narcotic, even the ones on the weak end like t3s and darvocets. IMO, to me thay act NOTHING like a narcotic. might be different for others.

angel

--------------------
"Some mornings, it's just not worth chewing through the leather straps."
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nycalt



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Re: Why is Tramadol in the same group as Opiates if its not one? [Re: AngelWolf13]
      #208498 - 12/17/04 03:20 PM

It is not a controlled substance (scheduled) like narcotics:

http://www.usdoj.gov/dea/pubs/scheduling.html

So, I am not sure what the origional person who started this thread meant.

It is NOT grouped with other opiates. Hence, why it is a lot easier to obtain than hydro, for example.

As far as people I know who had experiences with it, I have heard everything from it works, to it causes wierd outta body exeriences, to, yes, euphoria (and addiction) to it does nothing more than Advil (the most common).

From what I have read it was developed to be a stonger (than existing) nonaddicting, non-opiate substance that kills pain but doesn't have the "dangers" (addiction) of the opiate family.

However, "post marketing" experience indicates otherwise for many people. And its effectives vs. risk (Nader's Best Pills/Worst Pills has a "Do Not Use" on ultram/tramadol for example for this and other reasons) is highly debated.

There are several lawsuits (aren't there always) pending claiming that people got addicted to it despite manufacture promises that it is not addicting. I believe the manufacturer has stopped that claim at this point.

Nonetheless, it remains one of the strongest nonscheduled pain relievers, at least in theory.

Although I will say that man has yet to improve on nature when it comes to pain killers; opiates remain unequaled in their pain killing ability. Of course they also tend to cause euphopria leading to addiction and tolerance.

But don't blame the opium poppy. It didn't want to get eaten so it developed it's intoxicating/sickening/ sleeping ability to protect itself.

Most animals, looking for food, not to get high, realize after a good "nod" and a vomit this isn't the flower to mess with.

Humans, for better or worse, are more "intelligent" than this. In other words, on the positive side they have extracted the opium and proccessed/modified it in a variety of ways which began over 100 years ago with Morphine and resulted in a pain killer family that despite many past and continued (tramadol being one) attempts, it is still the most powerfull and effective and unequaled (usefull in almost all cases of pain).

But with the brain comes problems and adaptation mechanisims.

Humans also know, for example. that unlike their animal companions they "can get their food and get high too" and manage the stomach problem if they eat first; something the Poppy wasn't counting on....

Addiction is much more complicated than that, of course, but you get the point.

In any case, just to bring it back to Ultram to close, it is NOT grouped with the opiates because it is not one. It is grouped with pain killers, which is the class of drug it it is; so is Asprin. It doesn't mean anything more than that is what type of drug it is (its not an anti-depressant for example).

Tramadol works on the Serotonin system in the brain (totally different than opiates). But it's overall effectiveness and safety is highly debated.


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willygoat62
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Re: Why is Tramadol in the same group as Opiates if its not one? [Re: nycalt]
      #208508 - 12/17/04 03:55 PM

I had no effect even after 150mg.

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darcy34
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Re: Why is Tramadol in the same group as Opiates if its not one? [Re: willygoat62]
      #208514 - 12/17/04 04:19 PM

Different effects for different people. For me, it wipes out back pain and gives me energy. The downside is that it's definitely a little harder to focus on the task at hand and can cause mood swings. All this without being addicted? Is there anything that works as well for moderate pain w/o the side effects?

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sunflower29
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Re: Why is Tramadol in the same group as Opiates if its not one? [Re: darcy34]
      #208552 - 12/17/04 07:45 PM

I tried it once for my lower back pain and I felt great during the day, but woke up in the middle of the night terribly nauseous and I barely made it to the toilet in time. I was sick in bed the entire following day and it took me two days to feel somewhat back to normal.
Tramadol helped me so much for one day, but made me pay in a big way for two days. This was 100mg. I'll never take it again.
I've had the same thing happen with codeine, it makes me so sick, I'd rather endure the pain, so maybe my system just cannot tolerate opiates or medications that act on the body in a similar way as opiates.


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sharpie1
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Re: Why is Tramadol in the same group as Opiates if its not [Re: sunflower29]
      #208886 - 12/20/04 05:28 AM

As I understand it, Tramadol has some antidepressent action in the brain. I've taken them with excellent results. They do tend to give a different type of feeling than do the true opiates. I believe someone above posted somnething about it "raising the pain threshhold" As far as coming off this med I've read some real horror stories about it. Thank goodness when I came off it I only had a few days of mild flu like symptoms and that was it. I've heard of some people taking tramadol and hydro at the same time. My experience is that this is not a winning combination.

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seaofyouth
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Re: Why is Tramadol in the same group as Opiates if its not [Re: sharpie1]
      #208973 - 12/20/04 02:25 PM

I have been extremely addicted to it several times, I take something stronger now and have an appt. with a bupe doc on the 14th as I have hit my bottom with opiate addiction, but after 2 years clean of opiates I did relapse on Ultram, I remember the first time I took 1 and 1/2 , the euphoria was Godly.

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fiachat
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Re: Why is Tramadol in the same group as Opiates if its not [Re: piper65111]
      #208988 - 12/20/04 03:52 PM

It is not a scheduled med, but the docs treat it like one, and I once got into an argument with a nurse who insisted it was a narcotic and I couldn't get a refill without seeing the doc again. She even brought me her drug handbook, and I was able to point out to her that in fact Ultram is not scheduled. It does say that you should not prescribe it for a patient that had previously been addicted to narcotics. I guess it mimics addiction, I don't know. She felt stupid to say the least. I could not take it on a regular basis, like daily, as I had to increase the dosage. And it caused me to perspire excessively, something I don't normally do. Hated it and will never take it again.

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Julz
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Re: Why is Tramadol in the same group as Opiates if its not [Re: fiachat]
      #208992 - 12/20/04 04:21 PM

Ultram/Tramadol is VERY addictive. From what I've researched & read on other boards, wd's from Ultram can be and are worse than wd's from Hydro.
Ultram/Tramadol is also known to cause seizures. Just because it is not Sch. I, II or even III does NOT mean it is not a strong drug!

Peace,

Julz

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Love never fails. 1Cor 13:8

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Bamboo
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Tramadol in same group as Opiates its not [Re: Julz]
      #209008 - 12/20/04 05:00 PM

It's SOMETIMES in the same group as opiates, cuz it is only one molecule away from being an opiate. Altho it is NOT! Some peeps love it, some hate it. Everyone's internal chemistry is very different. Alot of peeps have been told that is IS a narcotic, because it's close chemically - but probably just told that for placebo effect. I've actually known peeps on Dog, who've used it to help w/withdrawals, but it has its own setbacks as well... I mean it does help some - but docs act like its MS or something; like they want u think it's a big deal!! Sure, I believe everything the FDA says, Vioxx is great, I mean, NO take Celebrex instead - NO i meant ...... uuuhhhh nevermind.
Please everyone - Make your own informed decision!


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sharpie1
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Re: Tramadol in same group as Opiates its not [Re: Bamboo]
      #209127 - 12/21/04 04:51 AM

Individual body chemistry plays a major part in how we react to drugs. With tramadol I get a mild buzz, with a feeling of energy. It will last much longer than a hydro buzz. If I run out of hydro then I start taking the tramadol and have absolutely no problems with wd's of any kind from the hydro. If I come off the tramadol I will end up with those mild flu-like symptoms for a few days then everything is fine. I am very grateful that I do not have the withdrawals I have read some folks endure. Doctors will tell you a lot of things about tramadol since much of their info comes from the drug reps. I've had one doctor tell me it is synthetic morphine, while another tells me it is absolutely a non-narcotic and not addictive. The former doc will only prescribe me about 30 a month, while the latter gives me 120 a month with six months of refills. Just try and guess which doctor I go see!!!

edited to add: Bamboo has given the best advice I've heard....research it yourself and make an INFORMED decision. The truth is out there!

Edited by sharpie1 (12/21/04 04:53 AM)


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avonmonnj
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Re: Tramadol in same group as Opiates its not [Re: sharpie1]
      #209281 - 12/21/04 03:13 PM

Tramadol has been found to have a positive effect on mood, but it was originally created as an ALTERNATIVE to opiates because of it's low affinity to receptors.

But every person is different. I get hardly any pain relief and no reaction from it, but from the addiction stories I've heard, I'm surprised the FDA hasn't rescheduled it. It's truly amazing.


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Thanatopium
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Re: Tramadol in same group as Opiates its not [Re: avonmonnj]
      #209362 - 12/21/04 07:31 PM

Whether it works for you or not, it is a mild narcotic, and it is built on the exact same frame as every other opiate drug in the world, bar none. All mimic the ultimate configuration of morphine to one degree or another, and tramadol is closer than many in this respect.
It does effect mu receptors, and it does produce analgesia throuhg this mecanism, as well as serving to increase level fo both serotonin and norepinephrine in the brain, producing elevated mood, and serving in the treatment of pain in this manner.

It is an opioid narcotic painkiller, there is no way around it.If it is an analgesic that is at least a partial agonist at the mu receptor site, it is an opioid.

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PJoseph
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Re: Tramadol in same group as Opiates its not [Re: Thanatopium]
      #209372 - 12/21/04 08:01 PM

This sounds completely far-fetched but it is true.

I wanted a non-narcotic pain reliever due to my job having policy that stipulates that if you get in an accident with a company vehicle or on company time you will be escorted to the hospital for an immediate pee test.

The doctor then prescribed me Ultram, saying it is not a narcotic so I can:
1.Operate heavy machinery-you know the label. lol!
2. Take prescribed dose during work hours.

Since this was the Company physician I never questioned him.
So, he whips out his prescription pad and proceeds to write the prescription for 1500, yes you read that right one thousand-five hundred.
I was astounded.
In fact, when I got to the pharmacy I asked them to break the script up to read 150 pills with 10 refills
See I told you you wouldn't believe me!

The point of my story is that there are some doctors whose only research on any paricular med is the Sales Pitch over donuts and coffee presented by the Pharm Rep.


Needless to say, I developed a little over-usage problem with Ultram.


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tone
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Re: Why is Tramadol in the same group as Opiates if its not [Re: Foxglove]
      #210070 - 12/24/04 11:07 PM

because people dont understand the difference between a mu opioid agonist as a mechanism of action and the opiate like chemical structure.

Does tramadol have a structure like the opiate type? No

is tramadol an opioid? yes, its metabolite mainly is.

methadone isnt an opiate type compound either, yet its a strong opioid.

people get these two confused...tramadol is not chemically related to opiates, yet its metabolite is an opioid by action.


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tone
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Re: Tramadol in same group as Opiates its not [Re: avonmonnj]
      #210073 - 12/24/04 11:15 PM

Quote:

but it was originally created as an ALTERNATIVE to opiates because of it's low affinity to receptors.




Itr true, tramadol has a very very low binding, 6000 times less than morphine, but its m1 metabolite is a different story. the m1 can only be formed by CYP2D6 where as virtually inactive metabolites are formed by CYP3A4.

i do not know why this is but tramadol is stronger and better for me than hydrocodone is. for some reason by body must form a lot more M1 and a lot less of the other metabolites. im lucky.

i believe tramadol should be started slow low and easy because some people get anxious from it and convulsive from it at higher doses.


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jazee
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Re: Tramadol in same group as Opiates its not [Re: PJoseph]
      #210106 - 12/25/04 10:07 AM

I'm curious to hear more details about your overuse problem. What was your average daily dosage and for how long? How did you come off it and what was that like?

The reason I ask is there really isn't a whole lot to choose from regarding pain killers that are easily obtainable over the counter or through a no-records hassle-free reputable domestic online pharamacy. Aspririn is hell for the stomach. Ibuprofen is weak and also can irritate the stomach and doesn't last very long. Tylenol can be bad for the liver at higher doses (over 1,000mg) especially if you consumer alcohol and has no anti-inflamatory effects. Naproxen Sodium just got clobbered by a big study showing it has negative effects on the heart in the long term. So for moderate pain relief with low risk of addiction, you're basically left with Tramadol as the only alternative.

So I've been using it for pain relief, even mild, and when I need anti-inflamatory I just combined it with ibuprofen. It works very well, and very long. Typically one dose a day is all it takes, 2 at the very most. The only downside of it is that it takes at least an hour to start to feel the effect, and about 2 hours before you get the peak benefits. I only take it ocassionaly in 50-75 mg doeses (couple times a week) and have had no side effects.

I can see the potential however to for my average dose to climb to 100mg when you're saying, gee this stuff works great, a bet if I take a little more it will work REALLY great. Because the drug is so easy to get and relatively cheap, I don't worry about running out of it either. So I do see an abuse/addiction potential but relatively much much lower than Codeine and some of the other opiates. However I am leary of the Serotonin effects this drug has as an anti-depressent over long term - I started another thread about that.

So what was your specific experience with this drug?


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avonmonnj
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Re: Tramadol in same group as Opiates its not [Re: tone]
      #210888 - 12/29/04 04:09 PM

I actually did have a convulsion after a day taking 50, then another 50, then a third 50mg caplet. Although I take other meds, I have been on them for years with no problems until I the tramadol. YES, this is a widely known side-effect - if your doctor won't discuss it - I would be very wary!

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Thanatopium
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Re: Why is Tramadol in the same group as Opiates if its not [Re: tone]
      #210970 - 12/29/04 11:28 PM

Tramadols structure is merely a streamlined opiate structure, with two of the cyclizations pared away. It is a simplified analogue of codeine, and is chemically related to the classic opiates in several different ways.

The reason it (and its metabolites) does have effects on the mu receptors is because it mimics the stereochemical configuration of codeine/morphine/etc. When you draw the molecules out in three dimensions, there are low energy configurations of tramadol that can be superimposed on the morphine skeleton.

The tertiary nitrogen, distance and number of bonds between it and the phenyl ring, the placement of the methoxy group, and its more active hydroxy derivative, if you examine the molecule closely you will find the morphine-type pharmacophores.

This hold true for virtually every chemical ever found to have activity at the opiate receptors, though some vary more than others.

Tramadol is actually much more like the classic opiates in structure than many of the other compounds with similar pharmacological activity. All narcotic medications have the same basic pharmacophores and can assume configurations spatially similar (a mild understatement) to the classic opiates, or more accurately, to endogenous peptides active at the mu receptors.


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tone
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Re: Why is Tramadol in the same group as Opiates if its not [Re: Thanatopium]
      #211655 - 01/01/05 07:46 PM

"Pharmacodynamics Ultram is a centrally acting synthetic analgesic compound that is not derived from natural sources nor is it chemically related to opiates."

- the tramadol prescribing info. http://www.opioids.com/tramadol/prescribe.html

thats why its 'not considered an opiate'


Hydrocodone

Morphine

Oxycodone

Codeine


-----

Tramadol


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tone
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Re: Why is Tramadol in the same group as Opiates if its not [Re: Thanatopium]
      #211668 - 01/01/05 09:44 PM

Quote:

Tramadols structure is merely a streamlined opiate structure, with two of the cyclizations pared away. It is a simplified analogue of codeine, and is chemically related to the classic opiates in several different ways.

The reason it (and its metabolites) does have effects on the mu receptors is because it mimics the stereochemical configuration of codeine/morphine/etc. When you draw the molecules out in three dimensions, there are low energy configurations of tramadol that can be superimposed on the morphine skeleton.

The tertiary nitrogen, distance and number of bonds between it and the phenyl ring, the placement of the methoxy group, and its more active hydroxy derivative, if you examine the molecule closely you will find the morphine-type pharmacophores.

This hold true for virtually every chemical ever found to have activity at the opiate receptors, though some vary more than others.

Tramadol is actually much more like the classic opiates in structure than many of the other compounds with similar pharmacological activity. All narcotic medications have the same basic pharmacophores and can assume configurations spatially similar (a mild understatement) to the classic opiates, or more accurately, to endogenous peptides active at the mu receptors.




good post. Its not like all the other semisynthetics and opiates though and thats what i meant


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Thanatopium
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Re: Why is Tramadol in the same group as Opiates if its not [Re: tone]
      #211671 - 01/01/05 09:55 PM

"Pharmacodynamics Ultram is a centrally acting synthetic analgesic compound that is not derived from natural sources nor is it chemically related to opiates."

I have read this, and others saying it is not chemically related, and seen many that say it is, including the orignal papers on its synthesis.

We could trade snippets all night, and it wouldn't really prove a thing...

I do understand what you are saying, and you are not "wrong" per se, but I just don't happen to agree with it.

I would love to redraw the pictures above into real three dimensional conformations, and superimpose the two molecules on top of each other... The similarities far outway the differences IMHO...

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Please, don't throw me into the briar patch...


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tone
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Re: Why is Tramadol in the same group as Opiates if its not [Re: Thanatopium]
      #211672 - 01/01/05 10:02 PM

and i understand what you are saying and you are not wrong per se either. the fact is, tramadol's m1 and m5 metabolites share attabutes with semi synthetics that make them have affinity for mu, however they arent like semi synthetics and thats probably where the idea of "its not an opiate" came from...

by the way , it IS m1 and m5 that are much much more of an opioid than tramadol. tramadol its self is a horrible nasty drug till it metabolises

a little interesting bit of tramadol trivia:

like with many other drugs, 3A4 enzyme tends to form inactive metabolites while 2D6 forms active. m1 and m5 are formed by 2D6 while the others, virutally inactive, are formed by 3A4:



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Thanatopium
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Re: Why is Tramadol in the same group as Opiates if its not [Re: Thanatopium]
      #211673 - 01/01/05 10:03 PM

http://www.fpnotebook.com/PHA33.htm

Tramadol
Ultram

1. Mechanism
1. Opiate analgesic (Codeine analog)
2. Weak mu-receptor binding
3. Inhibits Norepinephrine and Serotonin reuptake
4. Reported low abuse and addiction potential

http://members.aol.com/fibroworld/ultram2.htm

Tramadol is a synthetic analogue of codeine that binds to mu opiate receptors and inhibits norepinephrine and serotonin reuptake.


http://holivo.pharmacy.uiowa.edu/morphine/opioids_ringanal.pdf

Tramadol Analogue of codeine in which rings B, D and E have ...

http://cghane.netfirms.com/Su02.pdf
E. Tramadol (Ultam) 1. Background a. Opiate analgesic (codeine analog) active at mu receptor b. Reportedly low potential for abuse/addiction


A synthetic opiate, manufactured by Ortho-McNeil and marketed as an analgesic, Ultram has the potential for severe adverse side effects including seizures, convulsions, and anaphylactoid reactions.

uthor(s): Sunshine A, Olson NZ, Zighelboim I, DeCastro A, Minn FL
English Title: Analgesic Oral Efficacy of Tramadol Hydrochloride in Post-operative Pain
Source: Clin. Pharmacol. Ther. 1992; 51(6): 740-746.
Language: English
Substance(s): tramadol, paracetamol, propoxyphene, placebo
Data concercing tramadol:
Formulation/Appl.: capsule
Dosis: 75 mg, 100 mg
Frequency: single dose
Indication: cesarean section, obstetrics, postoperative pain
Adverse Event(s)/
Adverse Reaction(s): sweating, vertigo
No. of Patients: 80
Age Group: adult

Tramadol hydrochloride is a synthetic opiate agonist with a plasma elimination half-life of 5-6 hours and peak plasma levels at about 1.5 hours.


And so on, and so on, and so on...

From a structural analysts point of view, it is an opiate, anyone can disagree of course, and in the end, it is semantics... If it walks, talks and quacks like a duck, even if it does have less cyclic rings, its still a duck...

Dissenting opinions welcomed...


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tone
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Re: Why is Tramadol in the same group as Opiates if its not [Re: tone]
      #211674 - 01/01/05 10:06 PM Attachment (1 downloads)

hey check this out, tramadol's M1, (200 times more affinity for mu than tramadol)

Let me know what you make of that if you are into pharma chemistry



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tone
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Posts: 554
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Re: Why is Tramadol in the same group as Opiates if its not [Re: Thanatopium]
      #211675 - 01/01/05 10:13 PM

Quote:

Tramadol is a synthetic analogue of codeine that binds to mu opiate receptors and inhibits norepinephrine and serotonin reuptake.




tramadol, if you inhibit CYP2D6 is so so nasty its not even funny. its m1 and m5 that are good, so...


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