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  • N&PD Moderators: Skorpio | someguyontheinternet

MBDB toxicity

Well orgasm is generally a sympathetic act, potentially you just get a massive parasympathetic action following it...

Ah, I've just had an idea... That was rectal temperature right? Say at normal temperature, on MDMA you get X amount of vasoconstriction... but as the temperature drops, the brain gets a signal 'hey, your cutaneous sensors say it's actually quite cold' so the vasocontriction gets even stronger, pulling blood away from the rectal wall, leading to a drop in temperatures? It's a possibility...
 
That would only work if it was a surface that heat will be lost from, like the skin. A reduced blood flow to the rectum wouldn't work in the same way as it has nowhere to loose heat to. All it would effectively do is slow the temp probe/thermometer's response to a change in body temp.

Actually, the more I've thought about it, the idea of a conversion of normal protein to amyloid plaque prion doesn't sound that silly. If it only happened in neurons containing MDMA, that would specifically target the 5HT neurons (the first stages - reduction of dendritic projections - is similar).

I'm really tired now, so I apologize if when I look at this after waking up, it looks like so much gibberish



PS. I did a search on google about post=orgasmic flushing, and even when using the word serotonin as well, nearly all of the 1st 100 returns are for couples therapy, porn and penis enlargers (starts to bang head against wall to feel better!)
 
I had one last look, and found this (even if it's in a paper about allergic responses)

Paper at:
www.ovc.uoguelph.ca/BioMed/Courses/Public/ Pharmacology/pharmsite/98-409/notes/Inflammation.pdf

vasoactive amines: (from mast cells, basophils & platelets)
-histamine, 5-hydroxytryptamine (serotonin)
￾¨vasodilation & ￾ª vascular permeability


Similarly, forearm blood flow in response to serotonin-induced vasodilation was increased from baseline by a significantly greater extent after enalapril
Click to expand...

So serotonin does have vasodilation properties. That would fit with the hypothermia and hyperthermia as in the paper about the heat mediated neurotoxicity, it said the higher ambient temps were by placing the rat on a heat pad. Vasodilation in contact with one of those heat pads is going to cause an increase in body temp in the same way that vasodilation in a lower temp enviroment causes a reduction in body temp
 
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*Shrug* Rang Dale and Ritter says serotonin is vasoconstrictive... maybe it depends on what kinda blood vessel

I don't get your amyloid angle, there's no evidence for plaques in histological studies...

And vasodilation doesn't fit with increased hyperthermia at higher ambient temps.. increasing vasodilation will always drop, or keep core temp the same... if vasodilation at 30ºC plus caused an increase in core temperatures, then why do animals show vasodilation at high temps? All the people who live in places that get up to 40ºC would die from hyperthermia...

Or is this a sweat thing?
 
Or is this a sweat thing?

Yes. It involves the energy involved in latent heat of evaporation of water (sweat), the best way of losing heat being to get as much warm blood to the surface to facilitate evaporation of water (the latent heat involved is more than is required to up the same quantity of water be quite a few degrees centigrade - it's why alcohol feels cold if you blow on some on your skin).


The prion comparison is something that I just wondered about as both plaque formation and MDMA neurotoxicity both seem to go down the same route wrt the etiology of symptoms, but if they've already looked at that possibility, then it's back to the drawing board for me
 
Yes, I understand how sweating removes heat, but if, you suggested, cutaneous vasodilation, in hot temperatures, heats animals up, then animals would all die in ~37ºC environments.
 
No, that's where the latent heat of evaporation comes in. To turn liquid water at 37'C into water vapour at 37'C requires a lot more energy. The energy comes from the blood near the surface due to vasodilation. Just the act of water changing state ( from liquid to vapour) can reduce the temp of the blood by quite a few 'C. That means that causing water to evaporate in an ambient temp of 37'C can still reduce the local temp by quite a few 'C. Only if sweating is inhibited (at temps exceeding body temp) will the vasodilation cause the body temp to rise. Rats have very few cutaneous sweat glands, so that vasodilation on a heating pad (where the water can't escape very well), will transfer heat into the body, instead of away. The other ways that animals with less sweat glands lose heat is by pissing out warm urine, and replacing it with an intake of cooler water(the antidiuretic activity of MDMA effectively buggers that method) or positioning themselves in a stream of air to speed up evaporation (not much of that in a lab rat's enviroment)

Net result being that in a warm enviroment, and dosed with MDMA, is that the rat's body temp will go up
 
"Only if sweating is inhibited (at temps exceeding body temp) will the vasodilation cause the body temp to rise"

Are you saying that sweating is inhibited at 37ºC+ ?

And the problem with this whole theory is that people have shown MDMA to be vasoconstrictive in the ear and the tail, and people have shown that sweating increases with increasing MDMA... but I've never seen anything that shows increase vasodilation.
 
No, sweating takes place at all temps. I'm not doing a very good job at explaining myself.

Looking at the data graphs phase_dancer posted 26'C seems to be the temp that results in neither hypothermia or hyperthermia. Below that, and hypothermiia results, above hyperthermia results. This can only mean that the amount of heat exchanged with the external enviroment is the cause of the changes in body temp (colder ambient temps produce a more severe hypothermia). The main mechanism for heat exchange with the enviroment in mammals is vasodilation, so thats why I mentioned it.

Put another way

below 26'C heat out > heat in result hypothermia

at 26'C heat out = heat in result steady body temp

above 26'C heat out < heat in result hyperthermia

so it must be due to heat exchange with enviroment, as greater doses of MDMA only increase the tendancy expressed at the lower doses, and I can't think of any other significant method of heat exchange between a mammals body and the enviroment
 
I spy with my little eye and odd dose effect in the graph cited by Phase...

Look at the 20 and 22ºC graphs... the rat on 20mg/kg MDMA is effected way worse than the rat on 40mg/kg as far as hypothermia goes, but when it comes to hyperthermia, it's the other way around... maybe its a dual response... lower doses of MDMA cause a responce tending towards vasodilation (Serotonin mediated?) and then higher doses tend towards vasoconstriction (NA mediated)?

Check this shit from Rang Dale and Ritter:
The effect of 5-HT on Blood vessels depends on various factors, including the size of bessel, the scpeis , and the prevailing sympathetic activity. Large vessels, both arteries and veins, are usually contricted by 5-HT though the sensitivity varies greatly. this is a direct action on vascular smooth muscle cells, mediated through 5-HT2A-receptors. 5-HT also causes vasodilation by acting on 5-HT1-receptors, partly byu releasing nitric oxide from endothelial cells, and partly by inhibiting noradrenaline release from sympathetic nerve terminals. Thus 5-Ht2A-receptors predominantly give rise to vasoconstriction, whereas 5-HT1 receptors produce dilation...
...If 5-HT is injected intravenouisly, the blood pressure usually first rises, because of the contstriction of alrge vessels, and then falls, because of arteriolar dilatation.

This papers shows that presumabley large human hand veins contractile response to 5-HT is enchanced by cooling...

*Shrug*...
 
I saw a quote somewhere (I think on a page on heatstroke/sun stroke) that some ~70% of energy is lost by radiation rather than evaporative or conductive processes....

fastandbulbous -- another process is radiation ;). Conduction plays a role, but it's fairly minimal from memory.
 
Here we go:
http://www.emedicine.com/emerg/topic236.htm

The body's basal metabolic rate (BMR) is 50-60 kcal/h/m2 (approximately 100 kcal/h for a person weighing 70 kg). In the absence of adequate thermoregulatory mechanisms, the BMR may lead to an increase in body temperature of approximately 1.1°C/h. The rate of increase may be significantly higher during periods of heavy exercise or in the setting of high environmental heat loads.

Heat transfer to and from the body occurs via the following 4 mechanisms:

Conduction is the transfer of heat via direct physical contact; it accounts for 2% of the body's heat loss.

Convection is the transfer of heat from the body to the air and water vapor surrounding the body; it accounts for 10% of the body's heat loss. When air temperature exceeds body temperature, the body gains heat energy.

Radiation is the transfer of heat via electromagnetic waves; it accounts for most heat dissipation. As long as air temperature is less than body temperature, 65% of the body's heat is lost by radiation.

Evaporation is the transfer of heat by transformation of a liquid into a vapor; it accounts for 30% of the body's heat loss.

The body's dominant forms of heat loss in a hot environment are radiation and evaporation. However, when air temperature exceeds 95°F, radiation of heat from the body ceases and evaporation becomes the only means of heat loss. Evaporation of 1 mL of sweat results in the loss of 0.58 kcal of heat; thus, 1 L of sweat evaporated from the body accounts for the loss of 580 kcal of heat. An individual exercising in the heat easily can sweat 1-2 L/h. If humidity reaches 100%, evaporation of sweat is no longer possible and the body loses its ability to dissipate heat.
Click to expand...
 
Yeah, I was thinking that afterwards; it must be some combination of all those factors that come into play with regards to ambient temp and dose of MDMA that determines body temp. MDMA will also increase basal metabolic rate, so increased ambient temp would mean that the body has more heat to get rid of, but with less ability to do so.

How that alters all the different mechanisms of losing heat is obviously not just a simle model (sorry if this is a bit rambling - I need sleep, and to get rid of this cold!)
 
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