(01-02-2015 11:38 AM)DrHorrible Wrote:  Since this thread was revived, and I went through and read the whole thing, I just wanted to add something. It seems there are false connections being made between biological (in vivo) effects and pheromonal effects of chemicals. A common theme is the conjecture that if XXX promotes Z effect in the body, it should be tested for similar results as a pheromone. However, if you look at the most scientifically tested and proven human pheromones, at least the steroid ones, you'll find that these are the LEAST effective hormones in the body. The explanation for this is a simple evolutionary one. Sex steroids are metabolized (deactivated) by the body and excreted in sweat. Humans (among other animals) evolved a way to sense the presence of these sex hormone metabolites, which hint at the levels and balance of the hormones inside the body.

Real clues for pheromonal activity will likely come from theories of olfaction, assuming that olfaction and pheromone detection are similar. Receptor binding will likely explain most, but "vibrational" theory may have a role, too. These are very likely not the same receptors that are responsible for hormone and drug action. Either way, the molecular shapes (including conformers) and electron density will eventually predict pheromone activity, but just because we don't have that information now doesn't mean we should be connecting biological effects with the pheromonal. These effects of a single molecule are almost more likely to be opposite than similar.

^This^

In response to what Dr. Horrible wrote and Paradox bumped:

I would like to refer to a study i just put in the Pregnenolone thread.
It talks about how intranasally (inhaled) Pregnenolone and Progesterone have an effect on the emotional state of a person.
It also states that there is a large (24%) amount of inhaled molecule that ends up in the bloodstream.
It also showed which parts of the brain lit up for each molecule.
It also showed how different molecules vary in percentages for how they work their way into the blood & brain.


Here is an article about intranasal administration of Pregnenolone and Progesterone and the effects. It is awesome.

Quote:https://www.ncbi.nlm.nih.gov/pubmed/20570588
Brain distribution and behavioral effects of progesterone and pregnenolone after intranasal or intravenous administration.
----
Abstract

Neurosteroids hold great promise for the treatment of diseases of the central nervous system (CNS). We compared the uptake by 11 brain regions and appearance in blood of tritium-labeled pregnenolone and progesterone after intranasal and intravenous (IV) injection. Both neurosteroids appeared in blood and brain after either method of administration, but with important differences in uptake. Bioavailability based on appearance in arterial serum showed that about 23% and 14% of the intranasal administered doses of pregnenolone and progesterone, respectively, entered the blood. Brain levels were about two fold lower after intranasal administration for the two neurosteroids. With intranasal administration, brain levels of the two steroids did not vary over time (2-120 min), whereas brain levels were higher early (10 min or less) after i.v. administration. With i.v. administration, uptake by brain regions did not vary, whereas the olfactory bulb, hippocampus, and hypothalamus had high uptake rates after intranasal administration. Intranasal administration of prenenolone improved memory, whereas progesterone decreased anxiety, thus demonstrating that therapeutic levels of neurosteroids can be delivered to the brain by intranasal administration. The neurosteroids were rapidly degraded after i.v. or intranasal delivery, but pregnenolone was more resistant to degradation in the brain after intranasal administration and in serum after i.v. administration. These results show that either the i.v. or intranasal routes of administration can deliver neurosteroids to blood and brain, but that the two routes have significant differences with intranasal administration favoring some brain regions.

I will agree that the invivo effects of 'mones may be different than the pheromone effects, but I believe that the 2 types of effects will always have of chance of happening at the same time.

If a man has between 10-200ng/dL of pregnenolone in his blood on average, that would mean that if the average person has around 5L of blood that there is about 50dL, and as such for:
10ng/dL -> there is 0.5mcg of Pregnenolone in all 5L of blood.
200ng/dL -> there is 10mcg of Pregnenolone in all 5L of blood.

With this info.....
knowing that 24% showed up in the blood during this study....
A person could DOUBLE their blood concentration by inhaling between 2mcg-40mcg of Pregnenolone!

There would also be a significant amount of the molecule that does not go to the blood, but goes to the brain. Both effects can be had simultaneously by inhaling the 'mones.

(02-08-2017 6:05 PM)dexter Wrote:  In response to what Dr. Horrible wrote and Paradox bumped:

With this info.....
knowing that 24% showed up in the blood during this study....
A person could DOUBLE their blood concentration by inhaling between 2mcg-40mcg of Pregnenolone!

There would also be a significant amount of the molecule that does not go to the blood, but goes to the brain. Both effects can be had simultaneously by inhaling the 'mones.

Great citation!

DAMN STRAIGHT! There is pheromonal receptor activity, scent conditioning, and steroid/hormone analogs and bio-identical absorption (neuro etc) all going on across the spectrum in these mixes. Add to it endocrine response, molecular bacterial alterations, varying grades of purity and you've got yourself a huge array of variables.... and this is just the tip of the iceberg of possibility.

I know this publication and many others that confirm and elaborate those findings - and while I'm glad that Wiserd took the time to debunk the spreading of false information, in my opinion these are debates better taking place in private forums/groups or else mone-products get banned or vendors sued when the wrong people draw the right conclusions. Mones even act on nuclear receptors, regardless of what D. Horrible rationalised wrongly a few years ago.

And so do many aromachemicals by the way. And given the quantities used in perfumes, it is an interesting example on how an influential industry holds back info. It's a joke that perfumes do not have to openly state ingredients given that many musks have estrongenic activity, as one broad example. You'll end up with with quite some of it in the blood and brain, as wiserds calculations show. And the toll on the organism to metabolize/degrade those exogenous substances is probably much higher than the body metabolizing administred bio-identical hormones.

So, discussing these things openly is a two-edged sword for the phero-scene, to put it mildly.

(02-09-2017 4:25 AM)GoergeFocky Wrote:  So, discussing these things openly is a two-edged sword for the phero-scene, to put it mildly.

Goerge - I totally see the inference that "somebody is going to regulate Pheromones" as they have medicinal crossover possibilities".

There is totally a chance of it. Androsterone is on the Schedule III drug list in Florida next to codeine and anabolic steroids. So yes, they do ban some molecules already.

The flip side is also important. with Pregnenolone The human body contains between .5-20mcg in the blood, so why does the grocery store sell pregnenolone as a vitamin in 25-50mg/tablet, which is over 1000x the amount in the blood, in a single pill?

Well.... from "Chemical and Biological Aspects of Steroid Conjugation" edited by S. Bernstein, S. Solomon pg.234, the human body makes 14mg/day of Pregenenolone Sulfate. (this is Preg-s, not Preg, couldn't find the number for Preg)

14mg is way more, but the body is constantly metabolizing and using up the molecule as well. So although you can raise the blood levels of these molecules thru intranasal means, the effect is temporary as the body will use up the molecule and soon be back to the normal range. (i didn't have a half-life number for Preg or Preg-Sulfate, and I haven't figured out how to decode MCR "metabolic clearance rate" either... yet).

(02-08-2017 6:05 PM)dexter Wrote:  A person could DOUBLE their blood concentration by inhaling between 2mcg-40mcg of Pregnenolone!

I do not think they mean "inhaling" when they wrote about intranasal administration. I think they meant absorbing the steroid through the mucus membranes inside a person's nasal structures.

(02-09-2017 11:29 PM)metaltree Wrote:  I do not think they mean "inhaling" when they wrote about intranasal administration. I think they meant absorbing the steroid through the mucus membranes inside a person's nasal structures.

Yes, they used the steroids "dissolved in a proprietary oleogel". I'd wager though that inhalation goes the same route when the molecules are lipophilic.
And after all, mice are not humans, and some receptors and steroid-metabolizing enzymes are different in humans, certainly affecting the take-uu and action of inhaled Pheromones

Wiser, you're right, I forgot that there are pregnenolone and DHEA freely available in the US for example. Still, one could construct a case that with swallowing a pill you affect only yourself, sporting a phero-cologne you affect others and so forth ... as said, if regulations were based on logic, perfumes would have to be banned lng before that though ....

To come back to the purpose of the thread with these things in mind:

I wonder how Methyl-Salicylate behaves after inhalation. Brain Inflammation is associated with so many affective and neurological disorders that an anti-inflammatory (salicic acid) agent directly effective in the hypothalamus and hippocampus would seem promising. Methyl-Salicylate is a lipophilic volatile, so it might easily enter the brain. But what with the methyl-group there?

(02-10-2017 5:19 AM)GoergeFocky Wrote:  To come back to the purpose of the thread with these things in mind:

I wonder how Methyl-Salicylate behaves after inhalation. Brain Inflammation is associated with so many affective and neurological disorders that an anti-inflammatory (salicic acid) agent directly effective in the hypothalamus and hippocampus would seem promising. Methyl-Salicylate is a lipophilic volatile, so it might easily enter the brain. But what with the methyl-group there?

I had to look up Methyl-Salicylate. the fancy name for Wintergreen Oil. I was impressed that wikipedia listed it as a plant pheromone that plants use to signal each other.

So oil of wintergreen metabolizes into the salicic acid, the major metabolite of aspirin and has similar effects. It also (thanks to wiserds post in "mucosal absorption")
Prostaglandin E2 stimulates estradiol synthesis in the cerebellum postnatally with associated effects on Purkinje neuron dendritic arbor and electrophysiological properties.

Quote:Prostaglandin E2 stimulates estradiol synthesis in the cerebellum postnatally with associated effects on Purkinje neuron dendritic arbor and electrophysiological properties.

Treatment with cyclooxygenase inhibitors reduced cerebellar aromatase activity ... These findings reveal a previously unappreciated role for PG-stimulated steroidogenesis in the developing brain and a new potential route for inflammation-mediated disruption of neuronal maturation.

Soooo....... oil of wintergreen -> salicic acid -> reduce prostaglandin production -> reduce Estradiol synthesis -> change in person thru Estradiol being modulated

VERY INTERESTING GF!

(02-09-2017 11:29 PM)metaltree Wrote:  I do not think they mean "inhaling" when they wrote about intranasal administration. I think they meant absorbing the steroid through the mucus membranes inside a person's nasal structures.

I think it works both ways, through absorption in the nasal membranes and through absorption through the membranes in the lungs.

Quote:Absorption of Toxicants.
http://www.olemiss.edu/courses/phcl675/gentox2.pdf
Penetration and absorption of gases and vapors into the lungs:
gases and vapors come into equilibrium with blood in the alveolar capillaries almost instantaneously. This reflects Dalton's law of partial pressures, Henry's law (solubility of gases over a liquid), and the gases lipidaqueous partition coefficient.

Absorption of Aerosols by the lung
nonlipid soluble compounds the rate of absorption varies inversely with molecular size. Lipophilic aerosols pass epithelium rapidly. Also energy dependent transport systems in Type I and II alveolar cells.