Tricyclic's Analgesic Properties

[monstanoodle]

Last night I noticed myself aching for some reason and then remembered I'd had no Codeine all day.
I took approx. 90mg and waited. After a while I noticed that it wasn't as effective at relieving the withdrawal as I'd have hoped.
I shrugged it off and took the rest of my meds, which included Dosulepin (225mg).

I've read about Tricyclics being used for nerve pain. And I sort of remember reading that it's been speculated some may have a slight affinity for opiate receptors.
I've noticed a synergy between Codeine and Dosulepin before, and that is what happened last night. I got into bed after taking Dosulepin, still aching a little but feeling nicely calm. After a while the aches disappeared completely, leaving me very happy in bed - which is fairly unusual for me unless I'm very sedated.

Anyway, 'nuff ranting...
Has anyone else read a report about the ins and outs of Tricyclic's analgesic action?
Does it mention anything about Opioid receptors?
And why would there be so much synergy?

Thankya

 

[haribo1]

I don't think it's opiate activity. I was switched from opiates (which were not very effective) to amitryptamine and it worked wonders.

 

[MurphyClox]

The exact mechanism of Amitriptyline's analgesic properties (as one prominent tricyclic antidepressant) remains unclear.
Besides 5HT- & NE-reuptake inhibition, interactions for Amitriptyline are known with :
- opiod receptors (which?!)
- adenosine receptors
- block of alpha2-adrenergic, NMDA, nicotinic & muscarinic cholinergic and histaminergic receptors
In addition, it blocks various voltage-gated ion channels like K+, Na+, Ca2+
(Journal of Pain 2007, 8(7), p.549)

Some more detailed info about opioid receptor involvement: Amitriptyline showed around one fourth of the analgesic property of morphine in the mouse abdominal constriction assay.
(Br J Pharmacol 1998, 24(4), p.669)

Especially the second ref states a clear involvement of opioid receptors.

Murphy

 

[monstanoodle]

That's a bit of a tease isn't it...

Cheers though murphy.
I'd like to think there's ongoing research into this.
The other half of me thinks that there probably won't be more information for quite a while.

*Prays for more relevant quote throwings*

 

[MurphyClox]

Without refs this time:
I find some articles that suggest amitriptylines ability to block Na+-channels could be connected to it's analgesic properties, very much like oldschool lidocaine, but with longer persistency...As said before: There's no definite mechanism of action known.

 

[nleksan]

Would this account for Cyclobenzaprine's use as a muscle-relaxant? It is technically a TCA, if I remember correctly, but has a muscle-relaxant and somewhat of a pain-relieving effect (was recently in a bad car wreck and have a bad muscle injury all the way up and down my spinal cord, on both sides, and was Rx'd Flexeril along with narcotics for pain; even when taken alone, my back pain was noticeably reduced). I imagine it must have something to do with the NMDA receptor activity mentioned above, but the fact that actual analgesia was achieved made me think opioid-receptor agonist. No euphoria, and some people actually say cyclobenzaprine is dysphoric, so it could be a kappa-agonist (doing this from memory, guys, forgive any mistakes!) to some degree. That would explain analgesic effects in low-doses, but dysphoric and dissociative effects in high doses.

 

[vecktor]

Without refs this time:
I find some articles that suggest amitriptylines ability to block Na+-channels could be connected to it's analgesic properties, very much like oldschool lidocaine, but with longer persistency...As said before: There's no definite mechanism of action known.

the dogma is that TCA's work mostly by monoamine reuptake inhibition, there is certainly evidence that points in that direction but there are lots of things that don't quite fit.
indeed recently I read that amitryptyline may have utility in treating cystic fibrosis through reduction of ceramide levels in the lungs. I wonder what the reduction of ceramide levels does in the brain??? I would expect it to alter the properties of lipid membranes but what do I know.
So as time goes on I am sure we will find more and more of the drugs we thought we understood are doing other unxpected things. It is almost a case of the more we learn the less we know. which is why it is so interesting.

 

[Unlucky]

Triciylics like Amitryptiline are very commonly used in pain managment clinics for their pain releiving and analgesic properties, it was the very first thing they prescribed me for my joint pain when I went to one of these clinics.

I had also become curious also the first time I was prescribed it for pain and read that Amitriptyline is converted in the liver to the active metabolite nortriptyline. For nerve pain, the main mode of action is to increase descending inhibition of the spinal cord dorsal horn by affecting levels of noradrenaline and 5-HT. The modulation of the mKv1.1 K+ channel plays an important role in the central analgesia induced by the tricyclic antidepressants, clomipramine and amitriptyline. *2A-adrenoceptors appear to have a significant role in amitriptyline-induced acute analgesia in that *2A-adrenoceptors also participate in the sedative effects of amitriptyline.

Some additional information on the topic if you like....

http://www.anesthesia-analgesia.org/cgi/content/full/97/1/168

http://www.ncbi.nlm.nih.gov/pubmed/15381049

http://www.sciencedirect.com/scienc...serid=10&md5=76a8eab61b1a8827488956fc6fdba624

 

[MurphyClox]

the dogma is that TCA's work mostly by monoamine reuptake inhibition, there is certainly evidence that points in that direction but there are lots of things that don't quite fit.

Concerning the anti-depressant action, I won't disagree. This is accepted as granted.
I pondered more about the analgesic properties of TCA, in particular Amitriptylin.