http://www.ncbi.nlm.nih.gov/pubmed/25797832

An article that suggests hedione, which smells like jasmine and citrus, may have pheromonal activity.

I don't have the bandwidth for testing but thought others might be interested.

This is interesting. Structurally, hedione does have similarities that would suggest to me that it could bind to the same receptors as, say, androstenone or androstadienone. It has the conformational freedom and approximate size to achieve a similar shape. Even more interesting is that I have some hedione here...


FWIW I drew a hedione in a conformation that could conceivable share an active site with other pheromones.

(04-13-2015 9:11 AM)DrHorrible Wrote:  This is interesting. Structurally, hedione does have similarities that would suggest to me that it could bind to the same receptors as, say, androstenone or androstadienone. It has the conformational freedom and approximate size to achieve a similar shape. Even more interesting is that I have some hedione here...


FWIW I drew a hedione in a conformation that could conceivable share an active site with other pheromones.

Awesome. Very curious what you find.

Also, if you're looking for another lead, you may want to look at licorice scents. You've probably heard about this:

Quote:Among women who reported being extremely aroused by masturbation, every odor tested had an arousing effect. A Good & Plenty® licorice-based odorant and banana-nut bread combination (28-percent increase) and the Good & Plenty® licorice-based odorant and cucumber combination (22 percent) showed the greatest effect.

http://www.google.com/patents/US7067162

a number of licorice scent compounds look worth experimenting with:
Glycyrrhetinic acid (from licorice):

This molecule interacts with all sorts of hormone receptors, but is also relatively nonpolar at the right distance from the "A-ring" area, IMO.

acetanisole:

There's a related aldehyde used as well.

(04-13-2015 2:32 PM)DrHorrible Wrote:  Also, if you're looking for another lead, you may want to look at licorice scents. You've probably heard about this:

http://www.google.com/patents/US7067162

a number of licorice scent compounds look worth experimenting with:
Glycyrrhetinic acid (from licorice):

This molecule interacts with all sorts of hormone receptors, but is also relatively nonpolar at the right distance from the "A-ring" area, IMO.

acetanisole:

There's a related aldehyde used as well.

I tried making a cucumber seed extract based on that study a while back, and it made me horribly depressed.

Glycyrrhizic acid in licorice, for what it's worth, seems to interfere with 11beta HSD, similar to 7Keto DHEA. Maybe there's other activity as well.

I'm not sure what 11B hsd has to do with it. All evidence points to pheromonal effects to be VNO(or olfactory) cells directly influencing nerve fibers traveling to the brain. I'm not aware of any researchers who support an alternative view.

Quote:Inhalation of crystal androstadienone by heterosexual women activates the ventroanterior hypothalamus [33], an effect not observed in heterosexual men, in whom the same region is activated by estra-1,3,5(10),16-tetraen-3-ol, a substance similar to natural estrogen [33]. According to the authors, the effect as seen on PET scan is too rapid to be due to nasal vessel absorption; eliminating a possible systemic route, the observed activation thus suggests an olfactory contribution. Chronic anosmia due to polyposis abolishes the response to estratetraenol (estra-1,3,5(10),16-tetraen-3-ol).

Btw, I just glossed over the full text of that study. It made a few things clear:

1: The human VNO appears inactive. Known pheromone receptor interactions occur through pheromone receptors, but in the olfactory mucosa.
2: There are over 100 functional V1rs in the rat and mouse genomes, but only five intact vomeronasal-type 1 receptor genes (VN1Rs) are found in human and chimpanzee genomes (Liman, 2006). At least one of the five intact VN1R genes is expressed in cells of the human olfactory mucosa (Rodriguez et al., 2000).
3: Of the 100 compounds tested, Hedione was the most potent activator of the receptor, but other compounds also activated it -- see image.

The fact that so many compounds are so effective at activating this receptor, and that they are all relatively common fragrance ingredients these days makes me wonder how important "traditional" pheromones even are. Maybe it's just time to settle on a nice cologne? ;)

EDIT: Consider the implications regarding cover scents now. I've been told by women that AD's neroli scent is intoxicating, regardless of the mones added. The additive and multiplicative effects of these cover scents shouldn't even be in doubt anymore. They are present.

I'm not going to rotate these, because I have work to get to... However, imagine these rotated 180 degrees. Notice the carbonyl group (==O) and the relative size, shape, and polar areas of the molecule. I think you'll find it similar to androstenone/androstadienone/hedione. Also keep in mind that this is only 1 of 5 known pheromone receptors in humans. Perhaps alcohols (androstenol) and aromatic A-rings (estratetraenol), and sulfated androgens have activity on other receptors. Either way, it looks like we have enough evidence to derive some human VN1R1 pharmacophores.



EDIT: I can't edit the post with the image from the study, so I'll add it here: the labels on the two molecules (HED and MJ) are wrong -- they are reversed.

Thanks for the insights DrH. !
Like you, I feel these findings could have substantial scientific, pharmaceutical and commercial consequences in the long run.

At present, it should give the current phero-companies enough urge to look into their cover scents. It's no coincidence that some formulas are rumored to carry non-disclosed essential oils etc. - often where effects are not easily explainend by the Pheromones involved.