Posted by Sad Panda on January 31, 2004, at 9:12:21
In reply to Re: doxepin, remeron, whatever.. thread is off-top, posted by scott-d-o on January 29, 2004, at 14:44:47
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> you're prob right about that abstract, like most abstracts, it is poorly worded.;-) I think doxepin has only slightly higher affinity than mirtazapine for h1 (I think mirtazapine binds with a pKi value around 9 and doxepin has a pKi around 10), but doxepin is not as selective and has much stronger h2 antagonism, so I think overall it is much more antihistaminic.. but then again I'm already sick of talking about it.. i guess a lot of it depends on where u get your data from also.
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> scottHi Scott,
I'm not sick of talking about it yet :)
I don't know how strong Mirtazapine is at H2 antagonism, AFAIK H2 antagonism controls acid in the stomach, I'm only interested in H1 because of what it does for sleep. Stomach juice talk would be getting way off topic. ;)
Here is an article that says Mirtazapine is a potent H1 blocker & references the exact same paper by Fawcett J & Barkin RL. You can read it all at http://www.medscape.com/viewarticle/410902_print Here is a snip:
"Mirtazapine is also a potent antagonist at central and peripheral histamine (H1) receptors, which may explain its sedative effects. Unlike maprotiline, mirtazapine has little activity at muscarinic or peripheral a1adrenergic receptors.[1-4]
References
1. Holm KJ, Markham A. Mirtazapine: a review of its use in major depression. Drugs 1999;57:607-31.
2. Tetracyclic antidepressants. In: Olin BR, ed. Drug Facts and Comparisons. St. Louis: Facts and Comparisons. 2000:900-3.
3. Remeron® product information. Organon. April 1996.
4. Fawcett J, Barkin RL. A meta-analysis of eight randomized, double-blind, controlled clinical trials of mirtazapine for the treatment of patients with major depression and symptoms of anxiety. J Clin Psychiatry 1998;59:123-7."
Here is another snip from: http://www.psychotropical.com/notes/637.html"Mirtazapine (6-azamianserin) was, for good reasons***, first tested as a sedative around 1982 - 1985. It is of significance and interest to note one of the earliest papers in 1985; the title introduced it as a "new antidepressant" even though there was no evidence at that time of any antidepressant efficacy in humans. The paper actually investigated only the sedative effect. There is nothing like establishing the idea before the facts.
***good reasons:-- we now know it is the most potent anti-histamine on the world market, eclipsing even doxepin.""Like mianserin, mirtazapine is a potent H1 blocker (anti-histamine) and thus inevitably causes sedation and weight gain; indeed H1 blockade is the most potent property of both these drugs, mirtazapine being even more potent than doxepin."
"It is claimed to give relief from the ubiquitous anxiety symptoms of depression better and sooner than SSRIs, this is convincingly accounted for by its extremely potent sedative (and therefore anxiolytic) anti-histamine action. Indeed the first trial in 1985 was as a "pre-med" comparing its sedative / anxiolytic properties to diazepam. Mirtazapine 15 mg was equal to diazepam 10 mg."
Some receptor affinites from: http://www.psychotropical.com/notes/253.html
"Potency for blocking H1 and (A1) post-synaptic receptors
H1 blockade relates to a) sedation, and b) weight gain
A1 relates to postural hypotension and reflex tachycardiamirtazapine 0.12 (-)
Doxepin 0.2 (23)
Mianserin 0.4 (34)
Amitriptyline 1 (24)
Dothiepin 3.6 (450)
Nortriptyline 6.3 (55)
Clomipramine 15 (50)
Imipramine 37 (32)
Desipramine 60 (100)
Nefazodone 24000 (48)
trazodone 1100 (42)
Sertraline 24000 (380)
venlafaxine 35000 (35000)
Doxepin and mirtazapine are the most potent antihistamines on the world market, indeed, because of this doxepin has been marketed as a topical skin preparation."Mirtazapine is getting close to 2x stonger than Doxepin. People I have spoken with who have taken both say 15mg of Mirtazapine is about as potent as 25mg of Doxepin for sleep.
Here is another snip from http://www.biopsychiatry.com/
"Mirtazapine (Remeron) is a structural analogue of the off-patent mianserin (Bolvidon). It is a comparatively new drug - a so-called NaSSA. By blocking the inhibitory presynaptic alpha2 adrenergic autoreceptors and stimulating only the 5-HT1A receptors, mirtazapine enhances noradrenaline and serotonin release while also blocking two specific (5-HT2 and 5-HT3) serotonin receptors implicated in dark moods and anxiety. By contrast, stimulation of the 5-HT2A receptors accounts for the initial anxiety, insomnia and sexual dysfunction sometimes reported with the SSRIs; stimulation of the 5-HT3 receptors causes nausea. Unfortunately, mirtazapine is a potent blocker of the histamine H1 receptors too. So it tends to have a somewhat sedative effect. This profile may be good for agitated depressives and insomniacs."
Let me know if you want me to find some more info for you.Cheers,
Panda.
poster:Sad Panda
thread:306217
URL: http://www.dr-bob.org/babble/20040131/msgs/307653.html