Natural 5-HT1A Receptor Antagonists / Agonists / Ligands.

In my thorough (and somewhat exhaustive) research, I have come upon some particularly beneficial information. I have seen many people trying to find information on this topic, and it wasn't easy sifting through tons of information & studies in effort to compile an active list that can't be found on Wiki's 5-HT1A entry.


However now I have found what I believe to be the keys to what many of you search for.


A brief overview.

• Serotonin 5-HT1A presynaptic autoreceptors inhibit serotonin release, and noradrenaline release on sympathetic nerve terminals. (!) (!)
• Serotonin 5-HT1A agonists may decrease serotonin release, and this can be beneficial or detrimental, depending on your situation and genetics.
• Serotonin POST-SYNAPTIC 5-HT1A receptors are largely involved in neuroendocrine responses; it is deemed to be (generally) the POST-SYNAPTIC 5-HT1A receptors that release cortisol, ACTH and prolactin as well as growth hormone.  (!) (!) (!)
• 5-HT1A receptors also have differential effects on memory, with some functions serving to improve short term memory, and yet decreasing long-term memory and some declarative memory functions. (!) (!)
• 5-HT1A PRESNYPATIC activation inhibits GABA in the PVN (Paraventrical Nucleus) projecting to the Spinal Cord. (!)
• 5-HT1A POSTYNAPTIC are located on GABAergic interneurons. The effects of modulating GABA through this pathway would depend on the ratio of presynaptic vs PostSynaptic densities.  (!) (!) (!) (!)
• 5-HT1A activation inhibits Substance P. (!) (!)
• 5-HT1A activation also inhibits NMDA-channels and activity. (!)
• 5-HT1A POSTSYNAPTIC activation increases noradrenaline in the hypothalamus. (!)
• 5-HT1A receptors correlate with glutamatergic tone (generally inhibitory) and are well expressed in the hypothalamus. (!)

Natural (Herbal) Agonists and Expression Modulators of 5-HT1A Receptors

GINKGO BILOBA EXTRACT    

( http://www.ncbi.nlm.nih.gov/pubmed/8051617 )

( http://www.ncbi.nlm.nih.gov/pubmed/10080249 )

( http://www.ncbi.nlm.nih.gov/pubmed/1361545 )

:: GINKGO BILOBA :: Reverses aging related decrease of 5-HT1A receptors and can act as a 5-HT1A agonist - which can improve some aspects of memory and modulate serotonin activity.



Natural HERBAL (5-HT1A Receptor Modulator/Antagonist)




I find this one especially interesting, it acts at PreSynaptic 5-HT1A's as an agonist; decreasing serotonin levels, but yet at the 5-HT1A Post-Synaptics, it inhibits the activity and decreases serotonergic tone yet again. This is likely to contribute to the compounds anxiolytic effects as noted in the study. Also may account for it's positive effects on LH, Testosterone and Cortisol. (!) (!) (!)

Although it may raise serotonin through other mechanisms (like MAO-inhibition and effects on sigma and transporters) - this might be a valuable tool in modulating the serotonergic system when combined with other ingredients. If you are looking to treat PSSD (Post SSRI Sexual Dysfunction) Berberine is of additional use in another way; besides it's effects on 5-HT1A receptors. It inhibits and downregulates PDE-5 (the same enzyme Viagra,Cialis etc Target).

( Berberine effect on PDE-5 mRNA Expression )

Berberine also has notable nootropic effects. (!)

NOTE : Berberine has also been found to exert an effect on other serotonin receptors, namely it antagonizes 5-HT4 receptors as well. Making it a suitable remedy for treating PSSD yet again. 5-HT4 serotonin receptors are anxiogenic (anxiety provoking) and contractile (constricting) - thus berberine improves vasodilation by dual serotonin and PDE-5 antagonism.

http://www.ncbi.nlm.nih.gov/pubmed/16973340

Binding of STW 5 (Iberogast) and its components to intestinal 5-HT, muscarinic M3, and opioid receptors.

Simmen U1, Kelber O, Okpanyi SN, Jaeggi R, Bueter B, Weiser D.

Author information

Abstract

Clinical studies with the fixed herbal combination product STW 5 (Iberogast) have indicated an efficacy comparable to metoclopramide (5-HT(3) antagonist) and cisapride (5-HT(4) agonist) in functional gastro-intestinal diseases like functional dyspepsia (FD) and irritable bowel syndrome (IBS). Since serotonin (5-HT(3) and 5-HT(4)) and muscarinic M(3) receptors are known to play a central role in the etiology of FD and IBS, the extracts contained in STW 5 and several of their phytochemical components were studied in vitro for binding affinities to these receptors of the intestine. STW 5 inhibited the binding of (3)H-GR113808 and (3)H-4-DAMP to 5-HT(4) and M(3) receptors, respectively, about 10 times more potently than the binding of (3)H-GR65630 to 5-HT(3) receptors. IC(50) values for STW 5 did correspond to extract dilutions of 1:1000 (M(3) binding) and 1:2000 (5-HT(4) binding). In addition, STW 5 also potently inhibited the binding to opioid receptors with an IC(50) value of 1:2000. Of the nine herbal extracts contained in STW 5, the fresh plant extract of bitter candy tuft (Iberis amara) selectively inhibited binding to M(3) receptors, while ethanolic extracts of celandine herb and chamomile flower were selective to 5-HT(4), and liquorice root to 5-HT(3) receptors. Binding affinities to human recombinant 5-HT(3), 5-HT(4) and M(3) receptors were qualitatively similar to those of the corresponding intestinal receptors. The benzylisoquinoline alkaloid berberine had significant inhibitory action on 5-HT(4) and M(3) binding, showing IC(50) values of 40 ng/ml (100 nM) and 200 ng/ml (500 nM), respectively, but is present in the extract of celandine herb only in traces, so that also for the celandine extract a cooperative effect of several phytochemical constituents can be assumed. These in vitro data indicate that 5-HT(4) (to a lesser degree 5-HT(3)), muscarinic M(3), and opioid receptors represent target sites for the treatment of FD and IBS with STW 5 (Iberogast).