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3-methylfentanyl

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HumbleStudent:
I have been trying to gather information on 3-methylfentanyl and I have some questions that I cannot find the answers to.

1. What is the therapeutic index of 3-methyfentanyl?
2. I read on some german website that 3-methyfentanyl is highly hypnotic and toxic.  Is this true?

... and no, I have no interest in synthesizing anything.  Just so you know.

Thank you.

descent:
According to the first publication on the subject the Thepeutic Index (LD50/ED50) of methylfentanyl is 1662; of fentanyl - 255; morphine - 75.6; pethidine - 4.89. It can be read in J. Med. Chem. 1974, v. 17, No10, the exact page is 1050. By a strange coincidence I have the paper wright now on my desk. But this impressive and highly optimistic safety margin was obtained from rat data which, sincerely said, are a little more than useless when speeking about humans. All opiates, including fentanyls, are very different for humans (they feel them like ... like opiates) and for rodents (they feel them rather like stimilants). All fentanyl derivatives have a specific effect on humans, especially when introduced i.v. - transitory paralysis of breathing. It's not the usual opiate respiraty depression; with fentanyls it's brief but in many cases fatal. It is occuring only during I.V. administartion and you will guess that it is not the usual method for drug administration on lab rats but unfortunately is typical for humans. I have not used fentanyls myself but I have friends who have used simple fentanyl and they will be very sceptic on their high safety margin. At least in humans. Be very carefull when interpreting lab rat data!

Rhodium:
According to Casy & Parfitt's book "Opioid Analgesics", this article will contain all the data you want, in detail.

N-4-Substituted 1-(2-arylethyl)-4-piperidinyl-N-phenylpropanamides, a novel series of extremely potent analgesics with unusually high safety margin.
Van Bever WF, Niemegeers CJ, Schellekens KH, Janssen PA., Arzneimittelforschung. 1976;26(8):1548-51.
Medline (PMID=12771)

The intravenous analgesic activity and toxicity of a novel series of N-[4-substituted 1-(2-arylethyl)-4-piperidinyl]-N-phenylpropanamides was studied in rats. Onset, potency and duration of analgesic action were assessed in the tail withdrawal test and compared with the activity of fentanyl, (+)-cis-3-methylfentanyl (R 26 800), morphine, and pethidine. All compounds studied were found to be extremely potent analgesics characterized by an unusually high safety margin. Methyl 4-[N-(1-oxopropyl)-N-phenyl-amino]-1-(2-phenylethyl)-4-piperidinecarboxylate (R 31 833; lowest ED50 = 0.00032 mg/kg) is the most potent compound (10 031 times morphine). cis-Methyl 3-methyl-4-[N-(1-oxopropyl)-N-phenylamino]-1-(2-phenylethyl)-4-piperidine carboxylate (R 32 792) is the longest acting compound (more than 8 h at 4 times the lowest ED50) and N-[4-(1-oxopropyl)-1-[2-(2-thienyl)ethyl]-4-piperidinyl]-N-phenylpropanamide (R 33 352) is the shortest acting compound (0.74 h at 4 times the lowest ED50) of the 4-substituted fentanyl derivatives. N-[4-(Methoxymethyl)-1-[2-(2-thienyl)ethyl]-4-piperidinyl]-N-phenylpropanamide (R 30 730) was selected for further investigation. R 30 730 has a rapid onset of action and is 4521 times more potent than morphine at the time of peak effect; it has a relatively short duration of action comparable to that of fentanyl and its safety margin (LD50/lowest ED50 = 25 211) is unusually high.
____ ___ __ _

Sufentanil, a very potent and extremely safe intravenous morphine-like compound in mice, rats and dogs.
Niemegeers CJ, Schellekens KH, Van Bever WF, Janssen PA., Arzneimittelforschung. 1976;26(8):1551-6.
Medline (PMID=12772)

Sufentanil (R 30 730), N-[4-methoxymethyl)-1-[2-(2-thienyl)ethyl]-4-piperidinyl]-N-phenylpropanamide, is a chemically novel, highly potent and extremely safe intravenous morphine-like agent in laboratory animals. In mice R 30 730 i.v. is 2304 times more potent than morphine (hot plate ED50's: 0.0028 and 6.45 mg/kg, respectively). The i.v. safety margin of R 30 730 in mice is 1 : 6 679 (LD50 = 18.7 mg/kg). Under the same experimental conditions the safety margin of pethidine is 1 : 7.97, of morphine 1 : 34.9 and of fentanyl 1 : 454. In rats R 30 730 i.v. is 4521 times more potent than morphine (tail withdrawal test ED50's: 0.00071 and 3.21 mg/kg, respectively). The i.v. safety margin of R 30 730 in rats is 1 : 25 211 (LD50 : 17.9 mg/kg). Under the latter experimental conditions the safety margin of pethidine is 1 : 4.80, of morphine 1 : 69.5 and of fentanyl 1 : 277. In dogs R 30 730 i.v. is 2429 times more potent than morphine (apomorphine antagonism test ED50's: 0.00028 and 0.68 mg/kg, respectively). The i.v. safety margin in dogs is approximately 1 : 50 000, the LD50 being +/- 14.0 mg/kg. All morphine-like effects of R 30 730 are immediately antagonized by nalorphine. These pharmacological findings are relevant in connection to the increasing interest for use of morphinomimetics in anesthesia.


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Studies on synthesis and relationship between analgesic activity and receptor affinity for 3-methyl fentanyl derivatives.
Jin WQ, Xu H, Zhu YC, Fang SN, Xia XL, Huang ZM, Ge BL, Chi ZQ., Sci Sin. 1981 May;24(5):710-20.
Medline (PMID=6264594)

    In the present paper, the synthesis and analgesic activity (mice, i.p. hot plate test) of the derivatives of 3-methyl fentanyl are briefly described. Compound 7302, cis-N-[1-(2-hydroxy-2-phenylethyl)-3-methyl-4-piperidyl]-N-phenylpropionamide (cis: 3-methyl/4-N-phenylpropionamide) is found to be the most potent analgesic agent in this series synthesized by our laboratory (ED50 = 0.0022 mg/kg). The analgesic activity of 7302 is 28 times more potent than that of fentanyl and 6300 times more than that of morphine. The partition coefficients of 10 compounds in the series are determined by high performance liquid chromatography (HPLC) and their log p values are about 3. There are no regular relationships between the analgesic activity and partition coefficients. Study on the specific binding of 8 out of the above 10 compounds to crude synaptic plasma membrane (P2-fraction) of mouse brain demonstrates that there is an excellent statistical linear correlation (r = 0.998) between the analgesic potency and the specific binding affinity. The result shows that the analgesic potency of the derivatives of this series is mainly dependent on binding affinity for opiate receptor.

HumbleStudent:

HumbleStudent:
As some of you know, I'm writing a book(fiction) and it deals with conspiracies, drugs etc.

I just need confirmation on a few ideas... or is the idea too far fetched?

Although I've read this in posts (After using TFSE), I just need confirmation...

What if someone accidentally poured say 5 ml of liquid with a narcotizing dose of 3-methylfentanyl or something equally potent (carfentanil) on his or her skin, would the person become high etc. (ie. get the effects of the substance)?  My uneducated guess would be yes, he would as the amount needed is so small that it would be absorbed almost instantaneously.

Your help will be appreciated.  Thank you.

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