P A
Bluelighter
When administered to depressives in moderate dosages over short span of time, the antimuscarinic scopolamine elicits potent antidepressant actions in a manner similar to ketamine and its NR2B antagonist friends. Following a short period of sustained treatment, this effect actually persists, potentially for weeks after the final dose. This relatively recent and unexpected finding (about 4 years off) appears to lend a hefty level support to the supposedly outdated "cholinergic hypothesis" of clinical depressive conditions (which has been largely ignored due to the widely proliferated and apparently quite profitable "monoamine hypothesis").
However, if the pharmaclogic analogy can be directly extended to ketamine, the arylcyclohexylamines, and other 2B-subtype NMDA dissociatives, then the mechanistic explanation invoking M1 muscarinic antagonism falls far short of helpful with regard to Scopace's antidepressant actions: if this is indeed the true mediator of its efficacy, then why not atropine? Dramamine? Periactin? Or hell, even Benadryl? Or better yet, the tricyclic antidepressants themselves, all of which exhibit at least some anticholinergic activity, typically leaning toward affinities for the M1 receptors comparable to that of scopolamine [as evidenced by their nasty range of untoward anticholinergic side effects]? Aside from atropine, which obviously has not and will not be investigated for this indication, what clearly differentiates each of the above agents from scopolamine in this regard? I can't think of any reason why H1 antagonsim would eclipse or at all interfere with an anticholinergic's effects on the nervous system, and it doesn't appear to do so in the slightest when it comes to other cerebral consequences of muscarinic blockade (delirium, cognitive fuckups, amnesia), and this appears to be the only other common property among each listed drug, the tricyclics being particularly disturbing examples - if we've been using these drugs to treat depression for years, and all they've essentially been doing is something that could be easily reproduced with some Straterra and Sominex, then we may have been lost in the woods for quite a long while whilst the forest became less evident than the trees, in this case, the monoamines. If the results of this study are genuine, then monoamine reuptake inhibitors and other modulators are essentially a profound waste of scientists' time and consumers' cash as compared to powerful, selective anitcholinergics and, of course, ketamine. The difference in the case of scopolamine however, is profound - ketamine isn't likely to be extensively marketed or approved for what is essentially occasional p.r.n. (which many fools tend to read as "dangerous, uncontrolled, and recreational") use for depression due its popularized status as a powerful euphoric hallucinogen. Scopolamine doesn't enjoy such glamorized and stigmatized status, despite its colloquial moniker - Devil's Breath. Though it may be a potent deliriant in supra-therapeutic doses, it's popularly known as nothing more than the harmless, effective anti-motion sickness med, Scopace.
But this trial appears to have been largely ignored in the clinical setting, and outside of some scattered rat studies, I'm unaware of any subsequent human trials or replication of the results. Either 1) A old, but somewhat promising neurochemical hypothesis, a single study, and a bunch of anecdotes are simply wrong [somewhat likely], 2) Each of the drugs listed above have some common property (or even different properties) of which we're unaware that near-completely stifle/delay their 'should-be' efficacy as powerful antidepressants [still unlikely], or 3) Like ketamine and whatnot, they are all effective, quick-acting, and long lasting antidepressant agents, and have simply gone unnoticed or been ignored by the greater medical community [probably not]. In the end, when it comes to sever major depression, very few drugs are as powerful as they're so often touted to be, both in the literature and the clinic. We're now finally well aware that the SSRIs are little more than sugar pills with side effects for the indication for which they were first introduced, and I doubt the tricyclics and MAOIs are that much better. If this scopolamine trial and any other research it may spawn demonstrate further positive results, this could be a really big deal for a really big number of miserable people. Here's the abstract:
http://www.ncbi.nlm.nih.gov/pubmed/17015814
Please comment.
However, if the pharmaclogic analogy can be directly extended to ketamine, the arylcyclohexylamines, and other 2B-subtype NMDA dissociatives, then the mechanistic explanation invoking M1 muscarinic antagonism falls far short of helpful with regard to Scopace's antidepressant actions: if this is indeed the true mediator of its efficacy, then why not atropine? Dramamine? Periactin? Or hell, even Benadryl? Or better yet, the tricyclic antidepressants themselves, all of which exhibit at least some anticholinergic activity, typically leaning toward affinities for the M1 receptors comparable to that of scopolamine [as evidenced by their nasty range of untoward anticholinergic side effects]? Aside from atropine, which obviously has not and will not be investigated for this indication, what clearly differentiates each of the above agents from scopolamine in this regard? I can't think of any reason why H1 antagonsim would eclipse or at all interfere with an anticholinergic's effects on the nervous system, and it doesn't appear to do so in the slightest when it comes to other cerebral consequences of muscarinic blockade (delirium, cognitive fuckups, amnesia), and this appears to be the only other common property among each listed drug, the tricyclics being particularly disturbing examples - if we've been using these drugs to treat depression for years, and all they've essentially been doing is something that could be easily reproduced with some Straterra and Sominex, then we may have been lost in the woods for quite a long while whilst the forest became less evident than the trees, in this case, the monoamines. If the results of this study are genuine, then monoamine reuptake inhibitors and other modulators are essentially a profound waste of scientists' time and consumers' cash as compared to powerful, selective anitcholinergics and, of course, ketamine. The difference in the case of scopolamine however, is profound - ketamine isn't likely to be extensively marketed or approved for what is essentially occasional p.r.n. (which many fools tend to read as "dangerous, uncontrolled, and recreational") use for depression due its popularized status as a powerful euphoric hallucinogen. Scopolamine doesn't enjoy such glamorized and stigmatized status, despite its colloquial moniker - Devil's Breath. Though it may be a potent deliriant in supra-therapeutic doses, it's popularly known as nothing more than the harmless, effective anti-motion sickness med, Scopace.
But this trial appears to have been largely ignored in the clinical setting, and outside of some scattered rat studies, I'm unaware of any subsequent human trials or replication of the results. Either 1) A old, but somewhat promising neurochemical hypothesis, a single study, and a bunch of anecdotes are simply wrong [somewhat likely], 2) Each of the drugs listed above have some common property (or even different properties) of which we're unaware that near-completely stifle/delay their 'should-be' efficacy as powerful antidepressants [still unlikely], or 3) Like ketamine and whatnot, they are all effective, quick-acting, and long lasting antidepressant agents, and have simply gone unnoticed or been ignored by the greater medical community [probably not]. In the end, when it comes to sever major depression, very few drugs are as powerful as they're so often touted to be, both in the literature and the clinic. We're now finally well aware that the SSRIs are little more than sugar pills with side effects for the indication for which they were first introduced, and I doubt the tricyclics and MAOIs are that much better. If this scopolamine trial and any other research it may spawn demonstrate further positive results, this could be a really big deal for a really big number of miserable people. Here's the abstract:
http://www.ncbi.nlm.nih.gov/pubmed/17015814
Please comment.
