Kappa Opoid Agonist as HIV preventative

[senorsalvia]

There is an interesting post over at LadySalvia.net that has a story culled from Pub Med that is quite impressive....--    senorsal   (sorry I do not have the link handy)

[TooStonedToType]

Interesting.  If anyone gets the full article, please send it to me.  Thanks

http://ladysalvia.net/forum26/276.html

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http://www.bioportfolio.com/LeadDiscove ... 050208.htm

Kappa opioid ligands as underexploited treatments of HIV-1 infection

For those aged 25-44, HIV dropped from the leading cause of death in 1995 to third leading in 1996 and fifth leading in 1997. The age-adjusted HIV death rate of 5.9 deaths per 100,000 is the lowest rate since 1987; the first year mortality data were available for the disease. This dramatic reduction in AIDS related deaths has largely been due to the advent of anti-retroviral agents which prolong AIDS-free HIV infection as well as life-expectancy once AIDS has developed. Unfortunately the down side of this success is the appearance of drug resistance and consequently viral load eventually increases after prolonged and effective therapeutic intervention. Second line treatments should therefore be able to reduce the ability of HIV-1 to infect and replicate within host cells when viral load increases. Likewise treatments should also limit the development of HIV-related symptomology such as such as AIDS dementia. A small but convincing body of evidence suggests that kappa-opioid receptor agonists may meet both of these requirements. In 1996, kappa opioid ligands were reported to prevent HIV-1 expression in microglia.and consequent neurotoxic neural cell death. Kappa opioid ligands have also been shown to alter IL-6-induced HIV-1 expression in chronically infected promonocytes and HIV-1 expression in CD4 lymphocytes. Moreover opioid treatment has been shown to potentiate the efficacy of antiretroviral drugs. Most recently, kappa opioid ligands have been reported to inhibit HIV-1 entry into CD4 cells via down-regulation of CXCR4. Thus kappa opioid ligands demonstrate an exciting antiviral profile, blocking the ability of HIV-1 to infect and replicate within host cells and also preventing the neurotoxic effects of infection. This data suggests that kappa opioid ligands represent candidate adjuncts or back ups to standard antiviral therapies.

Link to Journal
http://www.ncbi.nlm.nih.gov/entrez/quer ... t=Abstract

[winder]

What is also interesting to realize is that when Daniel Siebert did his ligand screening to find out what receptor was responsible for Salvinorin's activity, he found that Salvinorin-A was comparable to potent synthetic kappa opioid agonists U50488 and U69593.

Potential natural AND synthetic HIV treatments...

[TooStonedToType]

There are several interesting pieces under the "Related Articles" link.  http://www.ncbi.nlm.nih.gov/entrez/quer ... d=11931835


This article seems to suggest a mechanism for some of the reports of salvia divinorum curing cocaine addiction.  I always thought She just scared the shit out of them so that they didn't want to do anything anymore.

*Kappa-opioid receptor ligands inhibit cocaine-induced HIV-1 expression in microglial cells.  http://www.ncbi.nlm.nih.gov/entrez/quer ... query_hl=2

[senorsalvia]

Guess the last entry should indicate that our Lady Sally is a keeper and coke is a no-no-eh??? :wink:   ----------------  senorsal

[laughingwillow]

Sally appears to have the ability to reset a craving mechanism which only becomes obvious when one has a desire to stop the behavior in question.

lw

[Stonehenge]

This will make it harder for the jerks in washington to make salvia illegal. It won't stop them but might give a few of them pause.

LW, I'm not sure I understand what you are saying about the craving mechanism. Does sally disrupt addictions like ibogaine?

[visionarybear]

very very interesting read
i intent to have a good ole read through a few more of those extracts after exams are over.
nice find
vb~

[TooStonedToType]

Go here and run a Find for "Salvinorin"
http://wiz2.pharm.wayne.edu/mediabstracts2005.pdf

Its nice to see there is some research being done.  Hopefully work with Salvia Divinorum won't be banned.  I would hope some of this would give them pause!  Austrialia's ban is sure looking more and more like a rash and uneducated decision.

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SYNTHESES OF KAPPA-OPIOID RECEPTOR LIGANDS: SALVINORIN A ANALOGS WITH MODIFICATION AT C-4 POSITION.

Salvinorin A is the most potent naturally occurring opioid agonist with a high selectivity and affinity for kappa-opioid receptor. . .

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SYNTHESIS AND EVALUATION OF SALVINORIN A ANALOGUES AS
KAPPA-OPIOID RECEPTOR LIGANDS FOR THE TREATMENT OF MOOD
DISORDERS.
Current treatments for depression and bipolar disorder require several weeks to become effective and often produce undesirable side effects. New drugs with improved efficacy, faster onset of action, and fewer side effects would revolutionize the treatment of these mood disorders. We recently reported that selective kappa-opioid receptor agonists produce depressive-like symptoms in rats, whereas selective kappa-antagonists produce antidepressant-like effects.

[JRL]

Anyone know more about salvia and cocaine addiction?

[senorsalvia]

Just had an appointment with my V. A. doc Tuesday..  Put me on Buproprion (for depression) that is widely toted as being a heavy anti smoking med;;;;;  NOT....  Then he asks me if I'm taking any hebals/non fda meds..  I tell him Salvia Divinorum.....  He has no idea...  I tellhim about how St John wort helped, but to a too small degree....    He gives me the rap about""But they aren't FDA approve/might cause interactions///   I told him I have been off Sall for a bit over 6 weeks, and for the first time since I went off VA head meds I have used Sally effectively, and now, here I am at the VA without my Sally and have to ask for antideppressants......    End result is senor now has a big bag of hEAD MEDS..    but====   THE DOC ASKED ME TO WRITE DOWN SALL'YS BOTANICAL NAME AND SAID HE WOULD GET ON THE  NET AND RESEARCH IT.........   SENORSAL

[laughingwillow]

You need some sally, sal?

lw

[Green2Herman]

People usually like the idé of Zyban since it works on the dopamin. It is thought to work on the reuptake of dopamin much in the same way as SSRI works on serotonin. Hence it decrease the derivata of the dopamin change, even out the changes of the amounts of dopamin over time (in regard to the amount between synapses). Hence why it is interresting for people who stop smoking since it will decrease to total number of minutes in which the dopamin are unusally low.

For medical conditions it is sometimes used for problems in the dopamin system such as ADHD, ADD and similar conditions, although it isnt very effective here. The reason for this being that it usually not increase the amount of dopamin to a normal level but rather remove times then it is unusuall low even for these people.

Sometimes for atypical depression it is tried and sometimes works. But it is important to understand that the result of Zymbian and similar drugs on major depression do not come near the result we get from SSRI, simple MAO inibitator as moclobemid or Tricyclic Antidepressants.

For depression after you have stopped drug use a combination of Zymbian together with an SSRI often are used with great help. The serotonin system can maybe in this situation be viewed as the slow wave of the dopamin system. The dopamin goes fast to a low level but get back to a level which can function resonable normal quite fast giving a long time feelt of insecurity due to the serotonin dropping during a long time, so it is a resonable combination.

[senorsalvia]

Ah me Brudda Willow; such a gracious offer is much appreciated!!        senor is going to stay off S.D. for the remainder of the time until my next appointment (one week from tommorow)  I promised the doc I would, with the caveat that if I felt the VA meds to be useless, then he would put into my VA file that I am self medicating because I percieve side effects of the meds to be not worth possible benefits......    (psssst, senor is shooting for a full VA pension ).......  senor still has about 3/4lb of stash, back at his place-      senorsal

[laughingwillow]

OK, man. You seem to be in possession of a plan. I hope it all goes swell.
Aside from the obvious, how do you perceive a full va pension as affecting your life style? Would you settel down into a more or less permenent residence? Travel like a moe-foe?

lw