DaveFoster
Member
The 5-HT7 receptor also has implications in circadian rhythms (and depression.)I tried to post this but forum has made it really ******* hard, it's frustrating. @haidut have you considered posting to multiple forums, or do you have a deal with charlie or some ***t? I don't hate him or anything but I am so sick of the internet. I'm out of energy for this ***t.
Anyway, I seriously believe lisuride could have major value as a regulator of circadian rhythms. 5-ht2c agonists apparently can emulate light signals: Serotonin 5-HT2c agonists mimic the effect of light pulses on circadian rhythms. - PubMed - NCBI And I've noticed personally that (although I did not enjoy lisuride's acute effects) lisuride seemed to improve ability to wake up at the right time. This has given it more value over time than metergoline, and I think that taking metergoline (or SSRIs) without lisuride to balance it out could be an error.
Agomelatine is a potential candidate for this argument: although the melatonin receptor agonism is obviously a strongly confounding factor, the 5-HT2c antagonism (as it's taken before bedtime) also suggests something for lisuride's usefulness. Agomelatine: A Novel Antidepressant
I would posit lisuride's ability to stimulate 5-HT2c while simultaneously making up for in dopamine agonism through other receptors, might make it a great candidate for fixing circadian rhythm issues.
If you took lisuride in the morning, and then took a combination of either agomelatine or GHB or baclofen (GHB is more physiologicially more appropriate than baclofen) and 5-alpha-DHP in the evening for the allopregnanolone, and at least 1-2 grams of glycine, could have potential solve anyone's circadian issues. To be clear the nighttime drug may require a combination of GABA-a and GABA-b drugs to be truly effective, as hinted by (this is about sleep paralysis in muscles during REM, however I think the interpretation is likely to extend to the other sleep mechanisms): Identification of the Transmitter and Receptor Mechanisms Responsible for REM Sleep Paralysis
(Although agomelatine has a rather good profile with non-5-HT2b-agonism, it can still give elevated liver enzymes)
I think lisuride could be an interesting pharmalogical alternative to agomelatine if used in the morning,.
@haidut
Do you know the approximate half-life of lisuride with SFA esters as a solvent? I'm calculating an equivalent 0.1 mg oral dosage with the different steady-state pharmacokinetics taken into account.
Also, do you think lisuride could cause serotonin syndrome in combination with other serotonergic antidepressants?
"...LSD and the novel ergot derivative lisuirde produced this syndrome in rats. These drugs possess both serotonergic and dopaminergic properties. Since changes in dopaminergic function have also been reported to affect the so-called serotonin syndrome, it was not clear how the two ergot drugs acted to produce this syndrome. The syndrome produced by pargyline and 5-hydroxytryptophan methyl ester was blocked by haloperidol, methysergide, parachlorophenylalanine, and alpha-methylparatyrosine; these treatments failed to block the effects of lisuride. Metoclopramide did not block the syndrome produced by either lisuride or pargyline plus 5-hydroxytryptophan methyl ester. Methysergide partially blocked the behavioral effects of LSD; pretreatment with either haloperidol or metoclopramide potentiated and prolonged the behavioral effects of LSD. The results suggest that dopaminergic modulation of the serotonin syndrome occurs before the serotonin receptor involved in this behavior. Also, the differences between LSD and lisuride may be relevant to their different psychopharmacological properties."
Reference: Lisuride and LSD: Dopaminergic and serotonergic interactions in the “serotonin syndrome”
Reference: Lisuride and LSD: Dopaminergic and serotonergic interactions in the “serotonin syndrome”
Last edited: