Posted by hello123 on January 28, 2015, at 21:08:16
In reply to Re: feeling like im out of options » hello123, posted by baseball55 on January 28, 2015, at 19:57:27
> The active ingredient in buprenorphine that can relieve depression is buproprion - an opiate. Naloxone (which is the active ingredient in naltrexone) is mixed with buproprion in order to prevent overdose or abuse of the drug by opiate addicts. The naloxone itself has no anti-depressant properties.
im referring to this med currently in Clinical Trials:ALKS-5461 is a combination of buprenorphine, a moderate partial agonist of the μ-opioid receptor (MOR) and antagonist/very weak partial agonist of the κ-opioid receptor (KOR),[9][10][11] and samidorphan, a selective antagonist of the MOR.[12][13] The combination of these two drugs results in what is functionally a selective blockade of KORs with minimal or negligible effects on the MOR.[13][11]
Through activation of the KOR, dynorphins, opioid peptides that are the endogenous ligands of the KOR and that can, in many regards, be figuratively thought of as functional inverses of the morphine-like, euphoric and stress-inhibiting endorphins,[14] induce dysphoria and stress-like responses in both animals and humans,[15] as well as psychotomimetic effects in humans,[16][17] and are thought to be essential for the mediation of the dysphoric aspects of stress.[18] In addition, dynorphins are believed to be critically involved in producing the changes in neuroplasticity evoked by chronic stress that lead to the development of depressive and anxiety disorders, increased drug-seeking behavior, and dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis.[14][18][19] In support of this, in knockout mice lacking the genes encoding the KOR and/or prodynorphin (the endogenous precursor of the dynorphins), many of the usual effects of exposure to chronic stress are completely absent, such as increased immobility in the forced swimming test (a widely-employed assay of depressive-like behavior) and increased conditioned place preference for cocaine (a measure of the rewarding properties and addictive susceptibility to cocaine).[20] Accordingly, KOR antagonists show robust efficacy in animal models of depression, anxiety, anhedonia, drug addiction, and other stress-related behavioral and physiological abnormalities.[14][15][21][22] As such, there has been great interest in developing KOR antagonists for the treatment of these and other psychiatric conditions in humans.[14][21] Progress has been limited until recently however, due to difficulty in finding selective KOR antagonists with suitable drug profiles (e.g., good pharmacokinetic parameters, short-acting KOR inactivation, lack of toxicity, etc.) for clinical development and use in humans.[15][21]
It has been known for decades that buprenorphine binds to at high affinity and antagonizes the KOR.[23][24] In addition, there have been many reports over the years supporting the idea of it being effective in the management of depressive and anxious symptomatology, and two small clinical trials have shown it to produce remission even in depressive patients refractory to conventional antidepressants and electroconvulsive therapy.[14][25][26][27][28][29][30][31][32][33][34][35] However, buprenorphine has never previously been seriously pursued for mental health indications, presumably due to concerns about its liability for abuse and dependence (and the additional difficulty in gaining regulatory approval that would certainly come with that).[36] In conjunction with samidorphan, as in ALKS-5461, however, its potential for abuse and dependence appears to be effectively negated.[37] As a result, it seems that ALKS-5461 may allow for buprenorphine to be employed safely and unrestrictedly in the treatment of depression and other conditions that it has shown efficaciousness in but that it would otherwise be used to treat likely only very rarely.
this is info from its Wikipedia article
poster:hello123
thread:1075467
URL: http://www.dr-bob.org/babble/20150102/msgs/1075685.html