New triple reuptake inhibitor antidepressant in the pipeline

[fastandbulbous]

It's a flavanoid in grapefruit juice that causes the inhibition (narangin I believe), and it does increase the activity of opiate drugs as it prevents the demethylation to normorphine/norcodeine derivatives (personal exp with dihydrocodeine & grapefruit juice REALLY surprised me as I was a doubter beforehand). All that's needed to really up the ante is something that induces CYP2D6; combine that with a 3A4 inhibitor and taking dihydrocodeine will be more like taking dihydromorphine

BTW is BL-2401 the company designation for thiorphan (or thiorphin), as that's the only enzyme inhibitor I've seen touted as promising for use as an analgesic

Now one thing I do know that potentiates opiates is DXM. It can remove tolerance and potentiate it.

I'd say ketamine is a much safer bet for reversing tolerance (no worrying little irks like serotonin syndrome)

 

[BilZ0r]

There's actually a whole array of chemicals in grapefruit that are cyp3a4 inhibitors: Regardé

 

[D_DOOD]

C6H6 - but I thought that growing more mu receptors is called down regulation and is one of the mechanisms of increase in opiate tolerance.

 

[BilZ0r]

Less receptors, or receptor affinity/efficacy is downregulation. More is upregulation.

 

[Ham-milton]

wow, this thread really veered off topic.

I'm jesus to this thread's lazarus-

anyway, has anyone heard anything more about this one?

 

[theantiadult]

wat about servector???supposed 2 b a pleasant sdri anti depressant

 

[hugo24]

DOV has gone bankrupt years ago,mostly because one drug was canceled as pain medication because inactivity (Bicifadine).

Is this the 3,4-Dichloroversion of (the 4-tolyl) Bicifadine drug?

 

[waterheart776]

There was something posted about grapefruit juice potentiating opiates. I would never have believed it but there does appear to be a method to the madness.

6',7'-Dihydroxybergamottin is the compound responsible, and yes, it is true. I've had several friends try it. Grapefruit juice increases the oral bioavailability of many CYP3A4 substrates (use your imagination)

On topic, this looks interesting. I'd be very interested to see the clinical trial results.

 

[waterheart776]

wat about servector???supposed 2 b a pleasant sdri anti depressant

Survector......not an inhibitor, a blocker. Totally different. Interestingly enough, I was just talking to someone about this a couple of weeks ago:

Amineptine (Survector) is a clean-ish, (relatively) selective dopamine reuptake blocker. Higher doses promote dopamine release too. Amineptine is pro-sexual and liable occasionally to cause spontaneous orgasms. It is a mild but pleasant psychostimulant and a fast-acting mood-brightener.

The compound was first synthesized by French pharmaceutical giant Servier. Licensed in France from 1978 under the brand name "Survector" and soon widely marketed abroad, amineptine is a clinically useful antidepressant. Unlike most other tricyclics, it doesn't impair libido or cognitive function.

Amineptine has a small but non-negligible abuse-potential. Its enjoyable but short-lived psychostimulant effect should be distinguished in clinical practice from its sustained antidepressant action. Arguably all too many contemporary "antidepressants" lack abuse-potential not through superior design or clinical efficacy, but because they aren't any good. The widely prescribed selective serotonin reuptake inhibitors (SSRIs), for instance, don't reverse the diminished libido and lack of interest in sex characteristic of (many kinds of) depression. Instead, SSRIs exacerbate the problem.

Unlike typical stimulants and other activating agents, amineptine may actually improve sleep architecture. Amineptine can be an especially valuable agent for melancholic, anhedonic and unmotivated people whose mood is sometimes worsened by SSRIs. Amineptine is also a useful agent in treating chronic "low grade" depression or dysthymia. There is little evidence of its value in anxious or agitated depression. Anxious depressives may do better on its chemical cousin, tianeptine (Stablon).

Amineptine isn't marketed or licensed in Britain and America. In Europe, too, the medication has been driven onto the pharmaceutical grey market. This is because FDA pressure led to the withdrawal of amineptine's EC product-license early in 1999, causing substantial problems for patients and physicians alike. In early 2005, Servier ceased production of amineptine in Brazil. It is still available in some Uruguayan pharmacies or as a research chemical, but the world-wide famine persists. Amineptine is off-patent, but not cheap. Optimal dosage is variable; but typically 100mg-200mg per day. No exact substitute for amineptine is currently on offer or in prospect....


http://www.amineptine.com/