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Lethal dose of a-PVP (research)

Brain

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A-Pyrrolidinopentiophenon is a synthetic stimulant, which is considered an analog of cathinone, the main component of the shrub Catha edulis. It is becoming more popular among people using psychostimulants. Depending on the nature of their terminal amine, alpha - and aryl substituent produce their effects according to the known mechanism of action by reuptake of various neurotransmitters. A pharmacological assessment of this action was carried out by foreign researchers to study the metabolism of these agents, to analyze the behavior along with the identification of loco motor activity, etc. However, toxicological study was conducted in minimal volumes and was mainly reduced to a retrograde analytical study of forensic aspects in overdoses by а-PVP and so on. Recently, scientific journals have been mentioning a lot of articles analyzing cases of acute poisoning and fatal outcomes in patients with present history of substance use, which can be considered a reasonable justification of relevance of present study. The aim of the study is to determine and to analyze data on acute toxicity in rats after intragastric and intraperitoneal administration of a-pyrrolidinopentiophenon.

The study was conducted on 144 male Wistar rats weighing 180-200 g. in accordance with GLP standards. The air temperature was 20 degrees Celsius in all cells, the conditions of detention were the same. The light/dark cycle, with a periodicity of 12 hours. The substance used: A-PVP(powder, 98.1% purity) 3 groups were identified with 6 subgroups (A1, A2, A3, A4, A5, A6; B1, B2, B3, B4, B5, B6 and C1, C2, C3, C4, C5, C6) of 8 rats in each subgroup according to dosages. Group A - the substance was injected intraperitoneally. Group B - the substance was injected through a gastric tube. Group C (control group) – intact animals that were administered equivalent dosages of 0.9% NaCl solution. A-PVP was dissolved in 0.9% buffer solution at appropriate concentrations.

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For LD50 registration Group A rats were administered the substance intraperitoneally at the following single doses: 200, 350, 450, 700, 900 and 1200 mg/kg. Group B rats received the substance via intragastric administration at doses: 300, 450, 600, 900, 1200, 1600 mg/kg. Group C received a 0.9% sodium chloride solution in equivalent doses.

Results and discussion.
Evaluation of toxic action of researched substance in experimental animals was carried out according to the clinical presentation of intoxication and survival rate. Results were determined using the method of (INITIALS) with LD50 statement. Fig.1. Intraperitoneal administration of the substance. Intragastric administration of the substance to Group B animals at doses ranged 300-450 mg/kg invoked the following clinical presentation: during 2 minutes breathing is dramatically more frequent, active grooming is manifested, there is urination, but no defecation, the rats drink water. After 50-80 minutes, the rats are moving moderately around the perimeter of the site, breathing is rapid, there is defecation(from 1 to 4 times), urination is active, repeated. After 120-200 minutes, the rats are moving slowly or moderately, breathing is rapid, there is no urination and defecation. After 250 minutes, the rats begin to move moderately around the perimeter, they begin to drink water actively, moderate grooming is manifested. These symptoms manifested in rats from Group A that received the substance intraperitoneally at doses of 200-350 mg/kg with different degrees of severity and duration, however, the beginning of the effects was significantly faster comparing to the Group B. So, after injection the clinical presentation remained during 30-40 seconds.

Animals of Group A(5,6), received 900- 1200 mg/kg., after injection fell into stupor for 30-80 seconds. (Fig. 2-4) Clinical indications included: breathing tachypnoea, significantly reduced reflex of the normal position when turning on the back. Ptosis and myosis were registered. There was no defecation and urination. After 10-15 minutes, the animal could not stand on its paws, it lay on its belly or on its side, breathing was frequent, intermittent, and shallow.

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Then, tonic convulsions occurred, within 70-100 seconds turning into convulsions caused by asphyxia (clonic, shortness of breath, cyanosis). Within 1 minute, death occurred. Clinical indications of subgroups B (5 and 6) were similar to subgroups A (5 and 6), however the severity of the indicators was less, and duration was longer. Death occurred within 40- 70 minutes. Organs (brain, heart, kidneys, liver, spleen) were removed from the dead animals for morphological studies.

Conclusion:

1. LD50 for rats weighing 180-200 g with intraperitoneal administration ≈ 410.8 mg/kg. For a human, this dosage is equivalent (with appropriate allometric coefficient) ≈ 86.4 mg/kg.

2. LD50 for rats weighing 180-200 g with intragastric administration ≈ 1093.0 mg/kg. For a human, this dosage is equivalent (with appropriate allometric coefficient) ≈ 262.3 mg/kg.

3. According to the results of conducted study, substance A-Pyrrolidinopentiophenon when administered intravenously should be attributed to class II (Highly hazardous).
 
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tonymontana2023

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Am admittedly confused

So to die from a-PVP a person like me who is 80kg would need to IM inject more than 6 grams? For a drug whose heavy dose is 25mg?

I am clearly missing sth here and can't deny that vaping pyros has depleted my brain of a further 20 iq points.

So I hope my question is not irredeemably stupid
 
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Brain

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Hi! If we assume a weight of 80 kg, the semi-lethal dose (LD50) is 5160 mg when administered parenterally. If you extrapolate the intraperitoneal administration of pirovalerone to rats and intravenous administration to humans, the semi-lethal dose is roughly 40% less and is about 3000 mg.
You were right to ask me this question.
I am willing to discuss any questions on this topic with pleasure!
 

tonymontana2023

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Hi! If we assume a weight of 80 kg, the semi-lethal dose (LD50) is 5160 mg when administered parenterally. If you extrapolate the intraperitoneal administration of pirovalerone to rats and intravenous administration to humans, the semi-lethal dose is roughly 40% less and is about 3000 mg.
You were right to ask me this question.
I am willing to discuss any questions on this topic with pleasure!
BrainThank you so much!

I smoke mdphp which I believe is at most equipment, and even 10mg get my bpm up to 140. 3g of it in one dose I don't even wanna think about

I wonder, I always get fear of heart attack with pyros. But I have never smoked more than 0.5g mdphp in a whole day.

If 3g is lethal dose in reality, does that mean this fear is just paranoia side effect from the drug?
 

tonymontana2023

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Thank you so much!

I smoke mdphp which I believe is at most equipment, and even 10mg get my bpm up to 140. 3g of it in one dose I don't even wanna think about

I wonder, I always get fear of heart attack with pyros. But I have never smoked more than 0.5g mdphp in a whole day.

If 3g is lethal dose in reality, does that mean this fear is just paranoia side effect from the drug?
tonymontana2023Equipotent * not equipment
 

Brain

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Yes, that is indeed fear. But don't forget that this fear is caused by the body's multiple regulatory systems, among them adrenal cortex hormones, which cause severe vasoconstriction of the coronary vessels, which can lead to acute myocardial ischemia and cause sudden cardiac death. I'm not scaring you, it's a fact.

So, I'm really asking you to be careful about high doses and frequency of use.
 

Frit Buchner

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Those are some tough rats! I doubt I would survive 1 gram administered by any means. The results of this experiment surprised me
 

Brain

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Those are some tough rats! I doubt I would survive 1 gram administered by any means. The results of this experiment surprised me
Frit BuchnerRats are really cool

With such high doses of stimulants, they can synthesize anything on their own (=
 

B3RS3RK

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But actually, that shit would probably kill a person, a rat would die at 0.1g at MOST
 

Brain

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This is only the semi-lethal dose (LD50)
In reality, the range may vary, just as the result of extrapolating the data to humans.
 
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