Involvement of Potassium Channels in Amitriptyline and Clomipramine Analgesia

http://www.ncbi.nlm.nih.gov/pubmed/11077073

http://www.sciencedirect.com/science/article/pii/S0028390800000976

Involvement of potassium channels in amitriptyline and clomipramine analgesia.
Galeotti N1, Ghelardini C, Bartolini A.
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Abstract
The effect of the administration of modulators of different subtypes of K(+) channels on antinociception induced by the tricyclic antidepressants amitriptyline and clomipramine was evaluated in the mouse hot plate test. The administration of the voltage-gated K(+) channel blocker tetraethylammonium (0.01-0.5 microg per mouse i.c.v. ) prevented antinociception induced by both amitriptyline (15 mg kg(-1) s.c.) and clomipramine (25 mg kg(-1) s.c.). The K(ATP) channel blocker gliquidone (0.1-1.0 microg per mouse i.c.v.) prevented antinociception produced by amitriptyline and clomipramine whereas the K(ATP) channel openers minoxidil (10 microg per mouse i. c.v.) and pinacidil (25 microg per mouse i.c.v.) potentiated tricyclic antidepressant-induced analgesia. The administration of the Ca(2+)-gated K(+) channel blocker apamin (0.1-1.0 ng per mouse i. c.v.) completely prevented amitriptyline and clomipramine analgesia. At the highest effective doses, none of the drugs used induced behavioural side effects or impaired motor coordination, as revealed by the rota-rod test, spontaneous motility or inspection activity, as revealed by the hole board test. The present results demonstrate that central antinociception induced by amitriptyline and clomipramine involves the opening of different subtypes of K(+) channels (voltage-gated, K(ATP) and Ca(2+)-gated) which, therefore, represent a step in the transduction mechanism of tricyclic antidepressant analgesia.

 

Danny, for the simple minded is your post suggesting amitriptyline could have positive affects on Tinnitus?

 

Well, there's already a study for that-

"Efficacy of amitriptyline in the treatment of subjective tinnitus.
Bayar N1, Böke B, Turan E, Belgin E.
Author information

Abstract
We investigated the effect of amitriptyline, a tricyclic antidepressant, on patients with subjective tinnitus. The study group consisted of 37 adult patients admitted to the Ear, Nose, and Throat and Audiology Department of Hacettepe University. The amitriptyline group consisted of 20 patients and the placebo group consisted of 17 patients. All of the patients were evaluated using a questionnaire, audiologic evaluation, high-frequency audiometry, impedancemetric tests, auditory brainstem response, tinnitus frequency, and loudness matching assessed by audiometric methods at the beginning and end of the study. The patients in the amitriptyline group received 50 mg/day amitriptyline in the first week and 100 mg/day for the following 5 weeks. In the placebo group, the patients received tablets consisting of lactose starch for 6 weeks, with a dosage of 1 tablet/day. The subjective complaints of the patients in the amitriptyline group decreased, and the "present" symptoms resulted in fewer complaints. The severity of tinnitus decreased in the amitriptyline group by means of subjective and audiometric methods. In the placebo group, no significant change was observed. The success of treatment was 95% in the amitriptyline group and 12% in the placebo group. Amitriptyline therapy was concluded to be effective."

 

Amitriptyline is a potent blocker of human Kv1.1 and Kv7.2/7.3 channels.
Punke MA1, Friederich P.
Author information

Abstract
BACKGROUND:
Kv1.1 and Kv7.2/7.3 channels control excitability of neuronal cells. As hyperexcitability is a sign of neuropathic pain, epilepsy, and anxiety disorders, these channels may be important molecular targets of amitriptyline that cause pharmacological as well as toxicological effects by altering neuronal excitability. Since the molecular mechanisms underlying these effects of amitriptyline have not been fully elucidated, we aimed to characterize the interaction of amitriptyline with human Kv1.1 and Kv7.2/7.3 channels. We also intended to establish the interaction of amitriptyline with the Kv7.2/7.3 channel opener, retigabine.

METHODS:
Kv1.1 and Kv7.2/7.3 channels were expressed in human embryonic kidney cells and in Chinese hamster ovary cells. The effects of amitriptyline and retigabine were studied with the patch-clamp technique.

RESULTS:
Amitriptyline inhibited Kv1.1 and Kv7.2/7.3 channels in a concentration-dependent and reversible manner. The IC50-value was 22 +/- 3 microM (n = 33) and 10 +/- 1 microM (n = 40), respectively. Deactivating inward currents of Kv7.2/7.3 channels were inhibited with an IC50-value of 4.2 +/- 0.6 microM (n = 32). Inhibition of Kv7.2/7.3 channels by amitriptyline reversibly depolarized the resting membrane potential. Retigabine reversed both the inhibitory action of amitriptyline on Kv7.2/7.3 channels as well as the depolarization of the membrane potential.

CONCLUSIONS:
Since amitriptyline inhibited Kv1.1 and Kv7.2/7.3 channels only at toxicologically relevant plasma concentrations, our results suggest a role for these channels in the neuroexcitatory side effects of amitriptyline. As the inhibitory effects of amitriptyline were reversed by retigabine, a combination of amitriptyline and retigabine could be of additional benefit in the therapy of neuropathic pain.

 

That is very interesting. Its a shame they are both such hardcore drugs. We know about Trobalt, but I think tricyclic drugs also come with quite severe sideeffects. But I need to take something soon as my T. seems getting worse by the minute.

 

Interesting, thanks Danny.

 

Started this Morning with clomipramine to fix my ocd. Maybe if the ocd is fixen and the anxiety is gone; my t will also calm down.

 

Let's keep in mind that amitriptyline is a potassium channel BLOCKER not a modulator.
I've actually tried it for a while, for headaches, since taking aspirin or panadol is no go for me, had absolutely no effect for the t.
Worked for the the headaches though.

 

Why aspirin and panadol? Aspirin is on ototoxic list, but panadol is not (as i know)

 

I am pretty sure I have read many times here on the forum that prolonged use of aspirin or high doses of aspirin can cause issues.
In any case, I try to avoid any kind of painkiller, your mileage may vary

 

For all members about pain killers, do not use aspirin or any ibuprofen drug, substance that can cause t in those drugs is Salicylic acid ! It is very hard to find any pain killer without Salicylic acid, but PANADOL is one of them without Sal.Acid, so safe for use!

 

I'am on 75mg Clomipramine since yesterday, increased dosage from 25mg to 50mg and now at 75mg. Yesterday I needed a pain killer (Naproxen) and had a spike last night.. However my reaction to T changed a bit.... It's seems to bother me not so much as a few days ago. So I hope the next few days it will improve even more..

Side effects at the moment:
- Minor restlessness
- Sweating
- Somewhat dry mouth

 

Ibuprofen does not contain salicylic acid..

 

Sorry, my mistake in sentence, both drugs aspirin (with salicylic acid) and ibuprofen could be bad for t. even to develop t in higher dosage. So almost all pain killer are harmful...beside Panadol as my pharmacist said (if I remember)....

 

If you want a painkiller I would try turmeric.

 

but there is no drug based on it...far as I know

 

Based on it? You can buy the powder or in-fact you can buy it in capsules. It's not a drug, but a natural product.

 

thats what I wanted to say, i have not seen that in capsules...\i Would definetly try to find it, if it realy works for headache...

 

It does and it also works for migraines.

 

So being on mirtazapine and clomipramine for a few months now. The mirtazapine seems to help with sleeping.

Clomipramine is fixing the depression and anxiety step by step.

One of them seems to increase my T a bit. However my reaction to it is getting better.