27 replies to this topic

[medievil]

http://en.wikipedia.org/wiki/Nefopam

Pharmacology

The mechanism of action of nefopam is not well understood, although inhibition of serotonin, dopamine and noradrenalinereuptake is thought to be involved in its analgesic effects,^[14][15][16] and there may be other modes of action such as through histamine H3 receptors^[17] and glutamate.^[18] Recently, like its analogue orphenadrine which also has analgesic effects, nefopam has been found to act as a voltage-gated sodium channelblocker, and this may in part or fully mediate its antinociceptive effects.^[19]

Interesting stuff.

Didnt really research wheter its a H3 antagonist but that gives it potential for other things too, honestly a night of research imprints a shitton of interesting meds, or meds that act on interesting pathways i cant get it properly posted and allways jump from one thing to the other, srry for lack of further elaboration but lets discuss it.

[xsiv1]

Where does it state that it can also possess anti-depressant activity? I see the results that indicate it may cause less respiratory depression.

[medievil]

Well its mao is screaming that out, ssri's are antidepressive, and dri even more due to da's implication in depression. And MU no comments needed.

[nowayout]

Tramadol (Ultram) is also an opioid/antidepressant combo.

[medievil]

But its not a DRI, wich is the most promosing route for antidepressant effects, also not a ssri, this is a sndri with mu agonism like perfect antidepressant profile, tramadol is a bit dirty. Dont know how euphoric the mu agonism is tough might be a bit too strong.

Will need dxm for tolerance issues.

Oh yeah tram was a sero releasing agent.

But also tram was one of those things a certain group of ppl respond too resistant to everything else.

[spermidine]

interesting.... and its uncontrolled in usa ? lol
what worries me, if it has any serious effect on opiod receptors and its addictive and potentially withdrawing is as bad in long term use. i dont like opioids at all and rather completely avoid but this one is enticing. wish someone experiments long term and report.

[medievil]

lol its cheap

wonder wheter i can get a script, perhaps from a addiction doc one gave me ascript for oxycodone for ocd once, said i ordered it online but couldnt afford anymore, with this one i could pull something offer it offered me better maintenance then methadone as it makes me feel "cured" with the doc thinking about its other property's, and say with low doses i refrain from abusing heroin.
Worth a shot


ACUPAN COMP 30 X 30 MG
nefopam
aktief product
Euro €8,63

[nowayout]

Well, to be honest, all opioids are good antidepressants. There are some comparative studies showing opioids to be more effective for depression than antidepressants.

[medievil]

But addiction risk is too high except in individuals with underlying opiate dysfunctioning that can take it without tolerance or addiction, either way ppl that respond to tramadol often dont respond to normal opies, this is another thing that can work for treatment resistant individuals that suddenly do respond to this.

[Doktor]

This is very interesting, coming from an individual recovering from a past torrid love affair with opiates. A few things:

1. Ok, so this opiate has DRI properties... but wouldn't it eventually become just as addictive as something like Tramadol?
2. If this drug does cause both psychological/physiological dependence with chronic use, why not just take a traditional opiate at a maintenance dose?

What I don't fucking understand is this: most people do not get adequate (or any) relief from currently marketed anti-depressants, and coming off of them causes a withdrawal symptom. Why the hell are we pursuing those avenues still? I think we need to begin looking at opioids as a possible solution... Why not an enkephalin inhibitor?

[medievil]

2. If this drug does cause both psychological/physiological dependence with chronic use, why not just take a traditional opiate at a maintenance dose?

because some might not respond to tramadol but will respond to this one, that simple.

Also selective serotonin releasers are another option, check my other thread for that.

[nupi]

It's not totally unheard of, either. Cymbalta is an analgesic SNRI (cousin of Tramadol if you want) that is actually FDA approved for Depression. I found it to be pretty nasty, side effect wise (worse than even Venlafaxine), though. And mixing it with booze resulted in rather nasty hang overs (so much for the analgesic)....

[nowayout]

Actually antidepressants have been used as analgesics for ages. Amitriptyline is an older tricyclic that is often used for analgesia at low doses.

[nowayout]

By the way, in case it appeared as if I was talking up Tramadol, that is not my intention.

I would not wish Tramadol dependence on my worst enemy. I take it periodically (at prescribed doses) for pain control (it really works better than other opioids IME), but the withdrawal when coming off is the pits. It is said to be worse than other opioids in this regard. I end up staying on much longer than needed because I can't face it.

i am pretty sure Nefopam will have a similarly awful withdrawal.

Edited by viveutvivas, 02 March 2013 - 03:09 PM.

[Doktor]

2. If this drug does cause both psychological/physiological dependence with chronic use, why not just take a traditional opiate at a maintenance dose?

because some might not respond to tramadol but will respond to this one, that simple.

Also selective serotonin releasers are another option, check my other thread for that.

Lol I guess my viewpoint is biased; I have a very hard time seeing how anyone could not experience anti-depressant effects from something like morphine. Also, I don't think the whole addiction argument is relevant if the person has a daily legal supply, but that's more of a moral/ethical issue I guess :/

Also, by selective serotonin releasers, are you referring to something along the lines of MDAI? That's an interesting idea, I have only read reports of recreational use for that one... but it was developed as an anti depressant potential. No neurotoxicity, but would it not at least down-regulate the receptors and become ineffective after chronic consumption?

It's not totally unheard of, either. Cymbalta is an analgesic SNRI (cousin of Tramadol if you want) that is actually FDA approved for Depression. I found it to be pretty nasty, side effect wise (worse than even Venlafaxine), though. And mixing it with booze resulted in rather nasty hang overs (so much for the analgesic)....

I know effexor is actually structurally very similar to Tramadol, and cymbalta is likely as well, and they both exert analgesic effects which are blocked by naloxone... However the tricyclics also have pain blocking effects which are mitigated by naloxone... Apparently the serotonin/norepinephrine systems are pretty closely linked to the management of endorphins, so they can actually mitigate pain responses similarly to opioids... but without all that fantastic euphoria.

Actually antidepressants have been used as analgesics for ages. Amitriptyline is an older tricyclic that is often used for analgesia at low doses.

Yup, often used to treat fibromyalgia.

[nupi]

Effexor might be structurally similar to Tramadol but the acute opioid effects are wholly absent (which I guess is why it became approved as AD). Same goes for Cymbalta, BTW. Neither of the two creates anything like Euphoria whereas I remember Tramadol at least occasionally did (I was using it once or twice for acute pain)

[medievil]

Effexor has been shown to bind to mu a bit but is minimal at best, mirtazepine does too and its proposed thats why the combo is better then most other combo's. Californian rocket fuel haha, its a bit too weak to call it that.

[nowayout]

Yes, Tramadol produces a pretty long-lasting euphoria. At first.

[Doktor]

Effexor has been shown to bind to mu a bit but is minimal at best, mirtazepine does too and its proposed that's why the combo is better then most other combo's. Californian rocket fuel haha, its a bit too weak to call it that.

Has it really? I was under the impression that it produced analgesic effects (which were eliminated by naloxone administration), but not necessarily by activating the mu receptors... tricyclics do exactly this.

A little off topic, but: http://www.ncbi.nlm....pubmed/17101991 <-- That look's amazing; potent analgesia, probably pretty euphoric, but apparently does not cause dependence or accumulate tolerance.

[medievil]

Effexor does activate mu but mildly yes.

Hmm interesting stuff, impossible to get i suppose?

[medievil]

J Pharmacol Sci. 2010;114(1):107-10. Epub 2010 Aug 10.
Antidepressant-like effect of venlafaxine is abolished in μ-opioid receptor-knockout mice.

Ide S, Fujiwara S, Fujiwara M, Sora I, Ikeda K, Minami M, Uhl GR, Ishihara K.

Source

Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Hokkaido University, Japan.

Abstract

Although the opioid system is known to modulate depression-like behaviors, its role in the effects of antidepressants is not yet clear. We investigated the role of μ-opioid receptors (MOPs) in the effects of venlafaxine, a serotonin and norepinephrine reuptake inhibitor, in the forced swim test using MOP-knockout (KO) mice. Venlafaxine reduced immobility time in wild-type mice (C57BL/6J), but not in MOP-KO mice, although no significant effects were observed on locomotor activity. These results suggest that MOPs play an important role in the antidepressant-like effects of venlafaxine.

Venlafaxine and mirtazapine: different mechanisms of antidepressant action, common opioid-mediated antinociceptive effects--a possible opioid involvement in severe depression?

Schreiber S, Bleich A, Pick CG.

Source

Department of Psychiatry, Tel Aviv Sourasky Medical Center, Tel-Aviv University Sackler School of Medicine, Israel.

Abstract

The efficacy of each antidepressant available has been found equal to that of amitriptyline in double-blind studies as far as mild to moderate depression is involved. However, it seems that some antidepressants are more effective than others in the treatment of severe types of depression (i.e., delusional depression and refractory depression). Following studies regarding the antinociceptive mechanisms of various antidepressants, we speculate that the involvement of the opioid system in the antidepressants' mechanism of action may be necessary, in order to prove effective in the treatment of severe depression. Among the antidepressants of the newer generations, that involvement occurs only with venlafaxine (a presynaptic drug which blocks the synaptosomal uptake of noradrenaline and serotonin and, to a lesser degree, of dopamine) and with mirtazapine (a postsynaptic drug which enhances noradrenergic and 5-HT1A-mediated serotonergic neurotransmission via antagonism of central alpha-auto- and hetero-adrenoreceptors). When mice were tested with a hotplate analgesia meter, both venlafaxine and mirtazapine induced a dose-dependent, naloxone-reversible antinociceptive effect following ip administration. Summing up the various interactions of venlafaxine and mirtazapine with opioid, noradrenergic and serotonergic agonists and antagonists, we found that the antinociceptive effect of venlafaxine is influenced by opioid receptor subtypes (mu-, kappa1- kappa3- and delta-opioid receptor subtypes) combined with the alpha2-adrenergic receptor, whereas the antinociceptive effect of mirtazapine mainly involves mu- and kappa3-opioid mechanisms. This opioid profile of the two drugs may be one of the explanations to their efficacy in severe depression, unlike the SSRIs and other antidepressants which lack opioid activity.

[nowayout]

Effexor has been shown to bind to mu a bit but is minimal at best, mirtazepine does too and its proposed that's why the combo is better then most other combo's. Californian rocket fuel haha, its a bit too weak to call it that.

Has it really? I was under the impression that it produced analgesic effects (which were eliminated by naloxone administration), but not necessarily by activating the mu receptors... tricyclics do exactly this.

A little off topic, but: http://www.ncbi.nlm....pubmed/17101991 <-- That look's amazing; potent analgesia, probably pretty euphoric, but apparently does not cause dependence or accumulate tolerance.

Why do you think it wouldn't produce dependence or tolerance? All opioids do, even endogenous ones.

[medievil]

Just the SNDRI effects of this alone make me interested, we havent got such compounds available for therapeutic use, naltrexone can be thrown in to inhibitit excessive addictive effects.

Anyone here knows anyone that got a script for this, is it considered a heavy duty opiate? will i get strange looks if i ask for a script? Or is it like tramadol considered the milder one's? altough im i can get anything prescribed with my doc manipulation skills haha.

Ill put myself in plaster and go ask saying i got it in uk with my uk passport after a car accident or something haha.

[Doktor]

Effexor has been shown to bind to mu a bit but is minimal at best, mirtazepine does too and its proposed that's why the combo is better then most other combo's. Californian rocket fuel haha, its a bit too weak to call it that.

Has it really? I was under the impression that it produced analgesic effects (which were eliminated by naloxone administration), but not necessarily by activating the mu receptors... tricyclics do exactly this.

A little off topic, but: http://www.ncbi.nlm....pubmed/17101991 <-- That look's amazing; potent analgesia, probably pretty euphoric, but apparently does not cause dependence or accumulate tolerance.

Why do you think it wouldn't produce dependence or tolerance? All opioids do, even endogenous ones.

I don't think that, the scientists in every article I have read sure do though. It has something to do with it's method of function. Endogenous and Exogenous opiates work by binding to mu among other sites, and this repetitive binding at higher levels is what causes tolerance. Apparently, by inhibiting enkephalinase, you can increase levels of endorphin's without causing an increase in tolerance. I believe I read that this is because there is an approximate threshold that endorphin levels must reach to kick in tolerance, and enkephalinase inhibitors will not cross this threshold.

Now, that being said, I have no idea how this substance could be a potent anagesic... again, these are not my thoughts/findings, rather they are those of the people who conducted the studies. Read up on any of the drugs in this class and you will see that none of them are known to cause tolerance, and many of them are purported to be stronger then morphine.

Also, if I had to hazard a guess, I am willing to bet that these drugs may be effective for pain, but are probably terrible for pleasure, and most likely come with a looooong list of side effects. Increasing endorphin levels in the brain does not necessarily mean instant opiate high.

[fool of light]

Hello guys.

Recently my girl had a surgery and as a post-surgery pain managment was offered 1g paracetamol or 2ml/20mg nefopam intravenous. Not knowing what nefopam was however knowing paracetamol on its own is shit and she's in terrible pain I advised her to take nefopam. She got 20mg-2ml. Did nothing to her,poor girl..anyway.

However reading a bit more about nefopam really interested me and it didn't take me more than 2days to get it from some local pharmacy (one of many reasons I love Asia) in its hydrochloride form 30mg a cap. Interesting is that it's 0 size cap (weighing roughly 100mg on its own) packed with white powder weighing more than 0.6g..will have to contact the manufacture and ask what other rubbish is inside...

Today was the day..have read everything I could on the internet starting with wiki finishing with some scientific comparative articles about nefopam and other analgesics (20mg equals roughly 12mg of morphine)..haven't found a single decent report of a recreational use of this thing at all..just bunch of some posts coming from people in terrible pain using it purely as a pain relief and the rest was just speculations based on it's triple reuptake inhibition and a possibility of having similar effect to tramadol hcl possibly enhanced in effect about some dopamine inhibition. Just to be clear here I love tramadol (125-150mg sweet spot) which I've in modesty been working with for more than a year by now. Some extra dopamine would hurt my experience I thought..Sooo..

As I mentioned my girl was given ridiculous dose 20mg intravenous..didn't help her at all..now I see that most of pain people posting their nefopam pain results taking 60-90mg 3x a day...ok, so having experience with doll(tramadol) and codeine lets try 90mg single dose almost empty stomach and clear head..

* t+0.5h feeling that sth's definitely coming..a bit like 150mg of t-doll t+3h..
* t+1h feeling pretty pleasantly heavy..however not as pleasant and natural I feel on doll..my appetite was totally gone,lying in beanbag felt like the best I could do and also not as mildly talkative like on doll..
* t+1.5h only though I have in head is about going to bed, off to bed I went..feeling more stable,enjoying melting - close to doll t+5to6h with some good smokes
* t+4h waking up feeling pretty much ok, slightly light but clearheaded overall pretty rested.
* t+5 feeling nefopam's gone...for the rest of the night with some minor sleep breaks Im taking care of my crying newborn babies with no sign of any negative emotional or physiological after taste but can't feel any positive uplifting afterglow like even t+10h on doll..
* t+12h getting ready to work feeling pretty good even though not much sleep at night.

Sooo...
What to say..I guess that most of you got a picture..let me try milder dose in a day or two thinking of 70-80mg single dose and I ll get back to you soon..

Take care till then...

[medievil]

Got a bunch 50mg tablets, just took one, im also on mpa/concerta atm tough.

 

Its medievil here, posting under this username now:)

[xks201]

Not so fast excess serotonin and opiate signaling can mimic a tranquilizer dart

[medievil]

never noticed anything but i was mistaken about its mu affinity unfortionally, srry guys

Got a bunch 50mg tablets, just took one, im also on mpa/concerta atm tough.

 

Its medievil here, posting under this username now:)