Sufentanil

Chemical Name N-[4-(Methoxymethyl)-1 -[2-(2-thienyl)ethyl] -4-piperidinyl] -N-phenylpro-panamide 

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Sufentanil [56030-54-7] (Sufenta), is five to ten times as potent as fentanyl. Sufentanil also has a short... 

Alfentanil, codein, dihydromorphine, etor-phine, fentanyl, heroin, hydromorphone, levo-methadone, morphine, oxycodone, pethidine, piritramide, remifentanil, sufentanil, tilidine, tramadol Buprenorphine, pentazocine Naloxone, naltrexone... 

Sufentanil, fentanyl, remifentanil, alfentanil, and morphine sulfate should be administered only by those specifically trained in the use of IV and epidural anesthetics Oxygen, resusdtative, and intubation equipment should be readily available. 

C,2oH2iiN20 61380-02-7) see Alfentanil iV-(4-methoxymethyl-4-piperidyl)propionaniIide (C15H24N2O2 61086-18-8) see Alfentanil Sufentanil 2-methoxy-5-(methylsulfonyl)benzoic acid (CgHioOjS 50390-76-6) see Tiapride 2-methoxy-10-[2-methyl-3-(p-toluenesulfonyloxy)propyi]-phenothiazine... 

The multiplicity of G proteins coupled to opiate receptors may explain how different opiates can bind to the same receptor yet induce different cellular responses. For example, morphine binds to the cloned rat fi receptor expressed in HEK 293, CHO and COS-7 cells and inhibits cAMP accumulation [80-82]. Morphine can be continuously applied to the cells for up to 16 h, and the potency and magnitude of morphine inhibition of adenylyl cyclase does not diminish [80, 81]. In contrast, the opiate sufentanil can bind to the same cloned fi receptor in HEK 293 cells to inhibit cAMP accumulation. However, sufentanil s actions rapidly desensitize [83]. Since both compounds bind to the same receptor, and the fi receptor is the only receptor these drugs can interact with in these cells, the ability of these two full agonists to differentially regulate the fi receptor must be due to their abilities to affect separate adaptive processes in these cells. 

Recent antisense studies have shown that knock down of Gi2 in mice-blocked morphine-induced analgesia, suggesting that morphine binds to fi receptors to activate G 2 to modulate neuronal circuits involved in analgesia [68, 84]. Sufentanil-induced analgesia was not diminished by Gi2 knock down suggesting that a different G protein mediated its behavioral effects [84]. 

Mutagenesis studies have shown that morphine and sufentanil bind differently to the jj, receptor [83, 85]. Mutation of an aspartic acid at residue 114 of the // receptor to an asparagine resulted in a mutant that did not bind morphine and morphine was ineffective in inhibiting adenylyl cyclase via that receptor. In contrast, sufentanil bound to the mutant and wild-type receptors equally well and it effectively inhibited cAMP accumulation via the mutant receptor. These findings demonstrate that morphine and sufentanil have different requirements for binding to the // receptor. By binding differentially, these two agonists may induce the ft receptor to interact with different G proteins to induce distinct cellular effects. 

Figure 16.5 Resulting pharmacophore for P-gp actively transported molecules. The depicted molecule is the analgesic (narcotic) sufentanil. The colored areas around the molecules are the GRID fields produced by the molecule yellow for DRY probe, green for TIP probe and blue for N1 probe. Reprinted with permission from ref. [53], Copyright 2005 American Chemical Society.

Sufentanil—also known as Sufenta , it is extremely potent (2,000-4,000 times more potent than morphine), and is used for heart surgery and childbirth. 

Tertiary arylacetamides appear to undergo hydrolysis to a very limited extent only. Hydrolysis of the synthetic opioid fentanyl (4.117) to despropa-noylfentanyl (4.118) was a very minor pathway in humans [76], No metabolites resulting from amide hydrolysis were detected for the fentanil analogues alfentanil (4.119) and sufentanil (4.120) [77], for which oxidative N-dealkylation was the main metabolic pathway. 

W. Meuldermans, J. Hendricks, W. Lauwers, R. Hurkmans, E. Swysen, J. Thijssen, P. Timmerman, R. Woestenborghs, J. Heykants, Excretion and Biotransformation of Al-fentanil and Sufentanil in Rats and Dogs , Drug Metab. Dispos. 1987, 15, 905-913. 

Russia remains secretive about this operation. Reporters learned that they drilled holes in the floor and used vents high on the wall to pump gas into the theater. Regrettably, however, they were unable to learn the precise nature of the gas, beyond the admission by a Russian scientist that it was a derivative of Fentanyl. Several highly potent drugs fit that definition, including carfentanil, sufentanil, alfentanil, remifentanil and etorphine. Any of these can produce anesthesia, lasting from minutes to hours. A Russian medical authority later added that they used 5x the effective dose in order to guarantee a rapid effect on the terrorists. It is not clear exactly what this means. 

Some observers speculate that the Russians used a drug unknown to the rest of the world to accomplish the theater rescue. Perhaps a combination of drugs was used. I found a research report that describes certain compounds that can partially block the respiratory depression, produced by sufentanil in rats, without interfering with the anesthetic effects. Dr. Stanley found this interesting but was dubious about its applicability to humans. It would be nice to have more data. 

Smoke now drifts down and spreads, gradually creating a uniform fog. Sufentanil alone might not be visible, but it is part of an aerosol made up of billions of very small dmg-impregnated particles. Without additional material to piggyback them, even distribution of the sufentanil molecules would be impossible. It s a fine science. Only in a size range of one to five microns - less than a tenth the diameter of a human nerve cell - will the particles reach the lower lungs, and stay there. 

SUFENTANIL CITRATE In obese patients (more than 20% above ideal total body weight), determine dosage on the basis of lean body weight. Reduce dosage in the elderly or debilitated. Monitor vital signs routinely. 

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