• What's so special about amitriptyline?

    Home Forums Chemically Correct Neuroscience/Nootropics What's so special about amitriptyline?

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    • #862508

      Ex Dubio
      Member
      QUOTE (KimberCT @ Jan 22 2010, 10:24 AM) [url=”index.php?act=findpost&pid=585728″][/url]
      I’m having a hard time figuring this one out. Amitriptyline and nortriptyline when added to my SSRI (haven’t tried them alone) immediately eliminate every trace of anxiety I have. I sleep better, wake up with energy, and don’t have that constant feeling of panic that I do without it.

      Unfortunately, they also come with nasty side effects. At 25mg I get chest pain, urinary retention, and epididymitis (?!).

      I’m trying to track down what is responsible for amitriptyline’s anxiolytic effect and/or what’s causing the side effects. I’m pretty sure it’s not a1 or 5-ht2c antagonism, nor norepinephrine reuptake since I’ve tried things like mirtazapine/mianserin, carvediol. Sigma receptor agonism? Channel blocking? Muscarinic receptor antagonism?

      Anyone here have any ideas?

      Amitriptyline has so many actions, you’re going to have a hell of a time pinpointing it. Here’s a few thoughts.

      Sigma-1 agonism: have you tried sertraline? Did it have effects that resembled amitriptyline?

      Sodium channel antagonism: ever tried any anticonvulsants like oxcarbazepine or lamotrigine? This are known for “brain-quieting” properties and function as anxiolytics in some.

      Calcium channel anagonism: kind of a far-fetched idea, but amitriptyline also hits Ca2+ channels; calcium channel blockers have shown some antidepressatn efficacy IIRC…ever tried one?

      NMDA antagonists: amitriptyline modulates NMDA at the same site as PCP, if I recall; ever tried other NMDA antagonists to compare effects on your neurophysiology?

      5-HT2C/2A, alpha1, H1 antagonism: compare with trazodone. If trazodone elicits similar anxiolytic effects, you can probably narrow down the probable pathways. If not, you still can eliminate these from the list.

      Then there’s the fact that amitriptypline agonizes the BDNF receptor binding sites, muscarinic receptors, and 5-HT6/7 receptors, the latter of which is simply not that well investigated.

      I figure you probably know most of this, but your best bet is to compare and contrast with drugs that more specifically target pathways activated by amitiptyline.

      Alternatively, if you want to go the polypharmacy route, try grabbing agonists of the receptors antagonized by amitriptyline and see if they reduce anxiolytic efficacy.

      #862515

      Anonymous

      Yeah, I’ve been going the trial and error route for awhile now without any luck and right now I’m looking for possible clues. I wasn’t aware of the NMDA antagonism. Maybe it’s time I finally add some DXM to my memantine.

      I have the following coming to me soon…

      Diltiazem for calcium channel antagonism. Oxcarbazepine for sodium channel antagonism. Trazodone for more 5-HT2 testing. Cyclobenzaprine because of its effects on the locus coeruleus.

      I have to locate some scopolamine to test the muscarinic receptors.

      I can probably rule out 5-HT7 as mianserin hits it with higher affinity than amitriptyline. Sigma-1 is a possibility. I haven’t tried sertraline, but I do take citalopram which I think is also a sigma-1 agonist.

      #862529

      Ex Dubio
      Member
      QUOTE (KimberCT @ Jan 22 2010, 01:22 PM) [url=”index.php?act=findpost&pid=585746″][/url]
      Yeah, I’ve been going the trial and error route for awhile now without any luck and right now I’m looking for possible clues. I wasn’t aware of the NMDA antagonism. Maybe it’s time I finally add some DXM to my memantine.

      I have the following coming to me soon…

      Diltiazem for calcium channel antagonism. Oxcarbazepine for sodium channel antagonism. Trazodone for more 5-HT2 testing. Cyclobenzaprine because of its effects on the locus coeruleus.

      I have to locate some scopolamine to test the muscarinic receptors.

      I can probably rule out 5-HT7 as mianserin hits it with higher affinity than amitriptyline. Sigma-1 is a possibility. I haven’t tried sertraline, but I do take citalopram which I think is also a sigma-1 agonist.

      Sounds like you’re on top of it. IIRC though, sertraline is something like a 10x stronger sigma-1 agonist than escitalopram/citalopram, at least at normal dosage.

      #862534

      Anonymous
      QUOTE (Ex Dubio @ Jan 22 2010, 03:51 PM) [url=”index.php?act=findpost&pid=585760″][/url]
      Sounds like you’re on top of it. IIRC though, sertraline is something like a 10x stronger sigma-1 agonist than escitalopram/citalopram, at least at normal dosage.

      Hmmm, I think I’ll give it a try… it shouldn’t be difficult to switch from citalopram.

      #862625

      Anonymous

      Afobazol is a sigma agonist, altough its also a MAOA inhibitor so you cant add it to a SSRI.

      #862626

      Anonymous

      Afobazol is a sigma agonist, altough its also a MAOA inhibitor so you cant add it to a SSRI.

      #862890

      Anonymous

      Well, looks like I can eliminate trazodone and atomoxetine from my list.

      I tried 20mg atomoxetine Friday night and it just made me sleepy and anxious… plus a decent headache the following day.

      I took 50mg trazodone last night. I thought this stuff was supposed to be sedating… I laid awake for a few hours before falling asleep. I felt like hell all day today which I imagine is due to the mCPP metabolite. I guess that means that 5-HT2C plays at least a partial role in my anxiety/brain fog.

      #862942

      Section 8
      Member
      QUOTE (Ex Dubio @ Jan 22 2010, 10:23 AM) [url=”index.php?act=findpost&pid=585736″][/url]
      Amitriptyline has so many actions, you’re going to have a hell of a time pinpointing it. Here’s a few thoughts.

      Perhaps because ‘pinpointing it’ is looking for a tree in a situation where the aesthetic appeal is derived from the forest as a whole.

      Phenomenological affect doesn’t correspond to any particular receptor site. In all likelihood, it’s some function of perception, memory consolidation and retrieval, turning the gears of allostasis. You see all kinds of “exciting new site-specific agents” come down the pipe-line; how many of them ever amount to shit? For depression, the cluster-fuck drugs, e.g., amp, MAOi, nicotine, etc., still reign supreme (though lamictal shows quite a bit of promise). Sedating TCA’s work awesomely well for anxiety, without the quasi-manic behavior that comes along with benzodiazepines.

      Personally, I think people need to focus more on fixing their lives than fixing their heads. What you see in these fora is just like Intervention, played over and over again… person gets isolated, treated, seems happy and fine; put them out into the day-to-day and suddenly “it stopped working.” A plant won’t thrive in toxic soil, no matter how much fertilizer you give it. Neither will people. People have preferences. When those preferences are frustrated, people experience distress. That’s just reality. Every time I see someone looking exceptionally hard inside, my eye wanders to their outside, and my evaluation is usually, “god.. who [i]wouldn’t[/i] be miserable living in those conditions?”

      #34343

      FadeIntoBig
      Member

      I’m having a hard time figuring this one out. Amitriptyline and nortriptyline when added to my SSRI (haven’t tried them alone) immediately eliminate every trace of anxiety I have. I sleep better, wake up with energy, and don’t have that constant feeling of panic that I do without it.

      Unfortunately, they also come with nasty side effects. At 25mg I get chest pain, urinary retention, and epididymitis (?!).

      I’m trying to track down what is responsible for amitriptyline’s anxiolytic effect and/or what’s causing the side effects. I’m pretty sure it’s not a1 or 5-ht2c antagonism, nor norepinephrine reuptake since I’ve tried things like mirtazapine/mianserin, carvediol. Sigma receptor agonism? Channel blocking? Muscarinic receptor antagonism?

      Anyone here have any ideas?

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