Lisuride

[BristolRob]

This is a long shot but anyone ever taken this compound?

 

[toxide]

this question is related to this compound but rather than start a new thread i'll just post it here...

So even at a high dose if this compound doesn't produce activity, based on the ways LSD breaks down over time does anyone think any of the breakdown products of Lisuride might actually be psychedelic? ....<probly a longshot to get an answer

 

[Ham-milton]

Isolated rat livers were perfused with an oxygenated saline medium containing 14C-lisuride. Metabolites obtained in the bile and the perfusate were characterized as the glucuronide of hydroxylisuride and hydroxy, 2-oxo, monode-ethyl, dide-ethyl, N6-demethyl and monode-ethyl- N6-demethyl derivatives of lisuride. In addition, the metabolite patterns were examined in various tissue homogenates in vitro and also in the rat in vivo. Whereas dealkylation reactions occurred predominantly under in vitro conditions, the metabolite profile observed in vivo was similar to that found in the perfused liver system. The principal routes for biotransformation of lisuride in the intact rats as well as in the perfused rat liver are those through aromatic hydroxylation and subsequent conjugation with glucuronic acid.

None of those sound potentially psychedelic. There's not much you can remove from Lisuride that can produce anything psychoactive.

 

[MeDieViL]

Bump, according to a egypt friend it was withdrawn there because ppl abused it.

Indeed, 8-OH-DPAT induced spontaneous 'tail-flicks' in the absence of external stimulation. This property was shared by lisuride and LSD, which also have high intrinsic activity at 5-HT1A sites.

Looks like its a potent 5HT1A agonist. I'm pretty interesting in trying this compound, even if it isnt a psychedelic.

 

[Psychedelic Jay]

Now if you mixed that with some 7-OH-DPAT, then you would be in total bliss.

 

[TheAzo]

Look at some of the other compounds that are HT1A agonists, most of them are NOT fun.

 

[MeDieViL]

Look at some of the other compounds that are HT1A agonists, most of them are NOT fun.

5ht1a: 4.00 5-MeO-MIPT, 4.00 lisuride, 4.00 DOET, 4.00 SS-2c, 4.00 5-MeO-DIPT, 4.00 DIPT, 4.00 5-MeO-DMT, 4.00 cis-2a, 4.00 DPT, 3.73 LSD, 3.61 mescaline, 3.59 RR-2b, 3.48 5-MeO-TMT, 3.45 TMA, 2.97 EMDT, 2.91 2C-E, 2.88 psilocin, 2.81 6-F-DMT, 2.75 2C-B, 2.38 MDA, 2.31 DOI, 2.20 2C-T-2, 2.04 4C-T-2, 1.79 2C-B-fly, 1.51 DOM, 1.18 DOB, 0.98 Aleph-2;

Those?

I know what your saying, but lisuride seems interesting to me.

 

[TheAzo]

Most anti-psychotics, and many antidepressants and similar are also HT1A agonists.
Psyches are HT1A agonists (as they bind to many of the same things serotonin does), but that's incidental, rather than central to their effects (as the good ones are also HT2A agonists)

In otherwords, i predict it will be a dud.

 

[acetylcholine]

Look at some of the other compounds that are HT1A agonists, most of them are NOT fun.

Perhaps lisuride has a higher intrinsic activity than the current azapirones like Buspirone or antipsychotics like Aripiprazole. I doubt a near-full agonist at 5-ht1a would be recreational, but it should have quite a different effect profile from partial agonists with low IA's.

The Egypt thing sounds like a fluke- if it was indeed banned, they probably banned it because of a structural similarity to LSD and rumors.

 

[/navarone/]

Shulgin wrote something about this compound IIRC.
He utterly disappointed that even though tests showed an almost identical binding profile to that of LSD, it did not produce any psychedelic effects.

Now, either there is some misinformation on what I know or someone needs to explain me this awkwardness.

 

[vecktor]

Shulgin wrote something about this compound IIRC.
He utterly disappointed that even though tests showed an almost identical binding profile to that of LSD, it did not produce any psychedelic effects.

Now, either there is some misinformation on what I know or someone needs to explain me this awkwardness.

there is a simple explanation involving agonist directed trafficking, which fits well with the availabe evidence. LSD invokes AA downstream signalling PLA2 I think Lisuride invokes IP turnover through the PLC-PI.

this is not new and has been well discussed out there.

 

[specialspack]

Bumping this... lisuride is often claimed as "lacking any psychedelic activity in man" but without reference e.g. this paper http://www.ncbi.nlm.nih.gov/pubmed/12373423

So I assume somewhere there are some subjective reports at varying doses?

 

[endotropic]

Bumping this... lisuride is often claimed as "lacking any psychedelic activity in man" but without reference e.g. this paper http://www.ncbi.nlm.nih.gov/pubmed/12373423

So I assume somewhere there are some subjective reports at varying doses?

I know this isn't exactly what you were looking for, but this was published in the lancet:

PSYCHIATRIC SIDE-EFFECTS OF HIGH-DOSE LISURIDE THERAPY IN PARKINSONISM

Sir, I regret deeply Dr Todes’ bad experience (July 5, p 36)
with the lisuride infusion pump. I support his conclusion that
psychiatrists ought to be included in any investigation of this system
(and of all other investigational studies of high-dose dopaminergic
therapy in neurological diseases). Todes suggested that the mental
side-effects resembled the effects of lysergide (LSD). We are
convinced that they are not caused by an LSD-like mechanism
affecting serotoninergic (5-HT) systems, but that they are virtually
identical with those seen with all forms of high-dose dopaminergic
therapy:
(a) Despite their chemical and biochemical similarities lisuride and
d-LSD have different effects on animals.1,2 In trained rats the
discriminative-stimulus effect of LSD (the LSD cue) is similar to
that of 5-HT agonists whereas the lisuride cue is similar to that of
the dopamine agonist apomorphine. 3
(b) In all our studies with healthy volunteers, we have not seen any
LSD-like hallucinations or similar effects.
(c) In clinical investigations in endocrine diseases, and after the
introduction of lisuride on the market as a prolactin-lowering
dopamine agonist, only 8 patients with psychiatric symptoms have
been reported to us. Furthermore, in none of them were the effects
LSD-like. Despite the high lisuride doses used sometimes--eg, in
the treatment of pituitary tumours-we have not learned of any case
of misuse of lisuride by those being treated with lisuride.

 

[ebola?]

Those?

How many of those listed are highly selective for 5ht1a? I would claim that we simply don't really know what a selective, full agonist would feel like.

ebola

 

[endotropic]

I would claim that we simply don't really know what a selective, full agonist would feel like.

ebola

A hypotensive crisis?

 

[specialspack]

Also - does anyone know where the functional data on lisuride can be found? Vektor says that lisuride favours IP accumulation over AA release, but I don't think it was tested in Parrish's thesis or any of the Nichols group papers that I can see.

 

[sekio]

Vektor says that lisuride favours IP accumulation over AA release

I read that too. Maybe it was the PLoS one study that gets cited over and over. I know there were measurements of 5ht2a/5ht2c intrinsic activity as well as Kis measured.

Also, anecdotal evidence: DPT makes my blood pressure fall like a stone, to the point of feeling faint in an upright sitting position(!). I wonder if e.g. buspirone has the same issues.

CBD is apparently a moderately selective 5ht1a ligand as well, displaces 8-OH-DPAT & produces similar response to serotonin and the anxiolytic effects of CBD are blocked by 5ht1a antagonists. For sure, CBD lowers blood pressure and produces "typical anxiolytic" effects. Given that CB2 agonists like e.g. caryophyllene are ... well, not psychoactive to my knowledge, even if they are anti-inflammatories, could the effects of CBD be attributed to 1a entirely?

Stimulant bonus round: Are there ergolines selective for 5ht1a? Are there "nonpsychoactive", say, flavonoids that bind 5ht1a?

 

[specialspack]

I read that too. Maybe it was the PLoS one study that gets cited over and over. I know there were measurements of 5ht2a/5ht2c intrinsic activity as well as Kis measured.

The Ray PLoS paper (I assume that's the one you're referring to) only measures accumulation of Ca2+, not IP or AA. On top of that the figures give Emax %s rather than intrinsic activities, i.e. doesn't take into account the tissue receptor density (is that correct...?).

So you get some pretty mad results - almost every substance is a full agonist, and a large number have Emax greater than 100%. One of the MDMA results comes in at 484% .

 

[endotropic]

Also - does anyone know where the functional data on lisuride can be found? Vektor says that lisuride favours IP accumulation over AA release, but I don't think it was tested in Parrish's thesis or any of the Nichols group papers that I can see.

I'd be very interested in seeing the evidence pointing towards the IP/AA theory myself. That one never really sat right with me.

 

[Hammilton]

Seriously? Fairly well established. And agonist directed trafficking is pretty much the only way to account for the fact that a few 5HT2a agonists just aren't psychedelic.