^Thats interesting. Any idea where I might go about finding info on the mirtazipine/psilocybin incident?
Edit: Did some quick searching and found a couple of interesting abstracts>
http://www.ncbi.nlm.nih.gov/pubmed/...ez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum
"Data now exist from which an accurate definition for serotonin toxicity (ST), or serotonin syndrome, has been developed; this has also lead to precise, validated decision rules for diagnosis. The spectrum concept formulates ST as a continuum of serotonergic effects, mediated by the degree of elevation of intrasynaptic serotonin. This progresses from side effects through to toxicity; the concept emphasizes that it is a form of poisoning, not an idiosyncratic reaction. Observations of the degree of ST precipitated by overdoses of different classes of drugs can elucidate mechanisms and potency of drug actions. There is now sufficient pharmacological data on some drugs to enable a prediction of which ones will be at risk of precipitating ST, either by themselves or in combinations with other drugs. This indicates that some antidepressant drugs, presently thought to have serotonergic effects in animals, do not exhibit such effects in humans.
Mirtazapine is unable to precipitate serotonin toxicity in overdose or to cause serotonin toxicity when mixed with monoamine oxidase inhibitors, and moclobemide is unable to precipitate serotonin toxicity in overdose. Tricyclic antidepressants (other than clomipramine and imipramine) do not precipitate serotonin toxicity and might not elevate serotonin or have a dual action, as has been assumed."
I wish it elaborated on 5-ht agonists. Let me see what else I can dig up...
This seems quite relevant>
http://www.ncbi.nlm.nih.gov/pubmed/...ez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum
"Recently, the addition of drugs with prominent 5-HT(2) receptor antagonist properties (risperidone, olanzapine, mirtazapine, and mianserin) to selective serotonin reuptake inhibitors (SSRIs) has been shown to enhance therapeutic responses in patients with major depression and treatment-refractory obsessive-compulsive disorder (OCD). These 5-HT(2) antagonists may also be effective in ameliorating some symptoms associated with autism and other pervasive developmental disorders (PDDs). At the doses used, these drugs would be expected to saturate 5-HT(2A) receptors. These findings suggest that the simultaneous blockade of 5-HT(2A) receptors and activation of an unknown constellation of other 5-HT receptors indirectly as a result of 5-HT uptake inhibition might have greater therapeutic efficacy than either action alone. Animal studies have suggested that activation of 5-HT(1A) and 5-HT(2C) receptors may counteract the effects of activating 5-HT(2A) receptors. Additional 5-HT receptors, such as the 5-HT(1B/1D/5/7) receptors, may similarly counteract the effects of 5-HT(2A) receptor activation. These clinical and preclinical observations suggest that the combination of highly selective 5-HT(2A) antagonists and SSRIs, as well as strategies to combine high-potency 5-HT(2A) receptor and 5-HT transporter blockade in a single compound, offer the potential for therapeutic advances in a number of neuropsychiatric disorders."
heres another interesting one>
http://www.ncbi.nlm.nih.gov/pubmed/...ez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum
"The novel antidepressant mirtazapine has a dual mode of action. It is a noradrenergic and specific serotonergic antidepressant (NaSSA) that acts by antagonizing the adrenergic alpha2-autoreceptors and alpha2-heteroreceptors as well as by blocking 5-HT2 and 5-HT3 receptors. It enhances, therefore, the release of norepinephrine and 5-HT1A-mediated serotonergic transmission. This dual mode of action may conceivably be responsible for mirtazapine's rapid onset of action. Mirtazapine is extensively metabolized in the liver. The cytochrome (CYP) P450 isoenzymes CYP1A2, CYP2D6, and CYP3A4 are mainly responsible for its metabolism. Using once daily dosing, steady-state concentrations are reached after 4 days in adults and 6 days in the elderly.
In vitro studies suggest that mirtazapine is unlikely to cause clinically significant drug-drug interactions. Dry mouth, sedation, and increases in appetite and body weight are the most common adverse effects. In contrast to selective serotonin reuptake inhibitors (SSRIs), mirtazapine has no sexual side effects. The antidepressant efficacy of mirtazapine was established in several placebo-controlled trials. In major depression, its efficacy is comparable to that of amitriptyline, clomipramine, doxepin, fluoxetine, paroxetine, citalopram, or venlafaxine. Mirtazapine also appears to be useful in patients suffering from depression comorbid with anxiety symptoms and sleep disturbance. It seems to be safe and effective during long-term use."
http://www.ncbi.nlm.nih.gov/pubmed/...ez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum
"This paper discusses how in vitro and preclinical in vivo studies might be of help for the interpretation and prediction of possible clinically relevant effects. The examples given refer to the data obtained with mirtazapine, a novel antidepressant with a dual mechanism of action, which can be best summarized as a noradrenergic and specific serotonergic antidepressant. Preclinical data on mirtazapine have shown that (i) its binding to plasma proteins is relatively low and non-specific; (ii) the contribution of its metabolites to the pharmacologic effect is negligible; (iii) it possesses high bioavailability, resulting in a low variance between individuals; (iv) it has no inducing or inhibiting effects on hepatic P450 enzymes;
(v) it has a very low potential for clinically relevant pharmacokinetic interactions with other drugs; and (vi) its disposition is independent of polymorphic CYP2D6 activity. The available preclinical data on mirtazapine could be used to advise clinicians and to guide clinical practice."
From what I've seen so far it seems mirtazipine is most likely to have high risk of interactions with other drugs that are substrate to CYP2D6 ie: DXM, 2c-e, 2c-t-2, 2c-t-7, etc. I cant find much yet on the metabolic pathway of 2c-t-4, but there is a chance CYP2D6 does have some role in the metabolism of 2c-t-4. More research is needed, but I'm not done searching just yet, this a pretty interesting topic
