Preparation of piperidine derivatives, sufentanil

[pHarmacist]

U.S. Pat. #: 5,489,689

http://patft.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PALL&p=1&u=/netahtml/srchnum.htm&r=1&f=G&l=50&s1=5%2C489%2C689.WKU.&OS=PN/5%2C489%2C689&RS=PN/5%2C489%2C689

----
Abstract

A piperidine derivative such as sufentanil is formed in a process which includes the step of condensing a piperidone with a primary amine so as to form a 4-amino-4-carboxyamino-piperidine.

...

Sufentanil citrate, first synthesized in 1974 (Niemegeers et al., Arzneim. Forsch. 26:1551-1556, 1976), is a piperidine derivative and a member of a series of potent fentanyl analogues. It is a powerful analgesic with an excellent safety margin as compared to other narcotic agents. It is furthermore characterized by a high selectivity and affinity (approximately 10 times greater than fentanyl) for "mu" opiate receptors...

...

...When compared with meperidine, morphine and fentanyl, in patients undergoing general surgery under balanced anesthesia, sufentanil provides stable cardiovascular parameters, low preoperative catecholamine plasma levels, very little need for additional inhalation supplementation, and a low incidence of postoperative respiratory depression.

Because of its remarkably low cardiovascular toxicity, sufentanil citrate has been evaluated as a total intravenous anesthetic for major surgical procedures.

EDIT:
Sufentanil, Potency: 20-30 x Fentanyl.
Fentanyl, Potency: 50-100 x Morphine.


1-2-3 ACiD

[Barium]

Patent US5489689

Catalytic hydrogenation freak

[Cyrax]

In humans, the analgesic potency of sufentanil is 5 to 7 times that of fentanyl.  The common epidural dose for fentanyl ranges from 25 - 100 µg, and for sufentanil from 10 - 30 µg

Sufentanil has a significant higher therapeutic index than fentanyl.  The following figures are from rat tail withdrawal tests:

Fentanyl:
 ED₅₀: 0.01 mg/kg
 LD₅₀: 3.1 mg/kg
 Therapeutic index: 277

Sufentanil:
 ED₅₀: 0.007 mg/kg
 LD₅₀: 18 mg/kg
 Therapeutic index: 26716

This explains why sufentanil is considered 'safer' than fentanyl (in the operating room, were one has a respiratory apparatus).

[pHarmacist]

I got the info on potency from this pdf:

https://www.thevespiary.org/rhodium/Rhodium/pdf/secofentanyl.pdf

(SCHEME 1)

1-2-3 ACiD

[Cyrax]

Yup, I see.

I 've got the "The analgesic potency of sufentanil is approximately 5 to 7 times that of fentanyl.  Dosage requirements for equianalgesic effect will be 1/5 to 1/7 those of fentanyl on a µg basis" information from

http://www.rxmed.com/b.main/b2.pharmaceutical/b2.prescribe.html

Unfortunately I can 't provide a link to sufentanil, because the search function on that site seems to be broken.  But search for 'Sufenta', when it 's fixed ... you will find a lot of usefull information.

Now that I 've thought a bit about it, it 's probably because sufentanil has such a high therapeutic index that they can administer relatively much of it (more than 1/20 - 1/30 of the fentanyl dose).

Other sufentanil info can be found at:

http://hsc.unm.edu/lifeguard/sufenta.htm

Furthermore, I checked my good old L'officine, Dorvault, 23 ^e édition.  And it says on p 116: "Le sulfentanyl est 5 à 10 fois plus puissante que le fentanyl".

This one says also: 10 x fentanyl

http://www.narcomed.com/books/opioide/sufentanil/indikationen.html#Dosierung

In rats, sufentanil seems to be 4800 times more potent than morphine.

http://www.narcomed.com/books/opioide/fentanyl/indikationsgruppe.html

Strange ... seems that rodents are more susceptible to sufentanil than humans ...  It's a shame that they can't do a tail withdrawal test on humans.
Hey, I've got it: insert the penis in water (brought up to 58 °C) & mesure the time before withdrawal   .  No, no ... Cyrax is just joking.  He 's in a rather funny state of mind   .

EDIT: Click manually on the 'S' and then on 'Sufenta'

[pHarmacist]

Now that I 've thought a bit about it, it 's probably because sufentanil has such a high therapeutic index that they can administer relatively much of it (more than 1/20 - 1/30 of the fentanyl dose).

of course hehe, how obvious


Furthermore, I checked my good old L'officine, Dorvault, 23 e édition.  And it says on p 116: "Le sulfentanyl est 5 à 10 fois plus puissante que le fentanyl".

hehe..



There Can Only Bee One - xX www.the-hive.ws Xx