Felypressin

Chemical properties

White or almost white, powder or flakes

Originator

Octapressin,Sandoz,W. Germany,1967

The Uses of Felypressin

Felypressin(Octapressin) is a vasopressin 1 agonist and a peptide containing eight amino acids including cystine. Felypressin is used as a vasoconstrictor.

Definition

ChEBI: A synthetic nonapeptide comprising cysteinyl, phenylalanyl, phenylalanyl, glutaminyl, asparaginyl, cysteinyl, prolyl, lysyl, and glycinamide residues in sequence, with a disulfide bridge joining the two cysteine residues. Its antidiuretic effects are less han those of vasopressin. It is used as a vasoconstrictor in local anaesthetic injections for dental use, and is an ingredient of preparations that have been used for treatment of pain and inflammation of the mouth.

Manufacturing Process

Preparation of N-Carbobenzoxy-L-Glutaminyl-L.Asparaginyl-S-Benzyl-LCysteinyl-L-Prolyl-ε-N-p-Toluenesulfonyl-L-Lysylglycinamide: 200 parts by weight of N-carbobenzoxy-L-prolyl-ε-N-p-toluenesulfonyl-L-lysyl-glycinamide are dissolved in 1,000 parts by volume of anhydrous acetic acid which has been saturated with HBr, the mixture allowed to stand for 1 hour at 20°C and then evaporated under reduced pressure at below 40°C. The residue from this evaporation is carefully washed with diethyl ether and then added to a solution of 185 parts by weight of N-carbobenzoxy-L-glutaminyl-L-asparaginyl- S-benzyl-L-cysteinyl-azide and 48 parts by volume of triethylamine in 1,500 parts by volume of dimethylformamide. The mixture is allowed to stand overnight at 20°C and the mixture is then poured into twice its volume of acetone. The precipitate which settles out is filtered off, washed with water, and recrystallized from dimethylformamide-acetone. There are thus obtained 190 parts by weight of N-carbobenzoxy-L-glutaminyl-L-asparaginyl-S-benzyl-Lcysteinyl- L-prolyl-ε-N-p-toluenesulfonyl-L-lysyl-glycinamide; MP 165°C (decomposition).
Preparation of N-Carbobenzoxy-S-Benzyl-L-Cysteinyl-L-Phenylalanyl-LPhenylalanyl- L-Glutaminyl-L-Asparaginyl-S-Benzyl-L-Cysteinyl-L-Prolyl-ε-N-p- Toluenesulfonyl-L-Lysyl-Glycinamide: 50 parts by weight of N-carbobenzoxy-Lglutaminyl- L-asparaginyl-S-benzyl-L-cysteinyl-L-prolyl-ε-N-p-toluenesulfonyl-Llysyl- glycinamide are dissolved in 400 parts by volume of anhydrous acetic acid which is saturated with HBr, and the mixture allowed to stand for 1 hour at 20°C. After evaporating off the solvent under reduced pressure at a temperature of 35°C (or another temperature below 40°C), the residue is carefully washed with diethyl ester, whereupon a solution of 32 parts by weight of N-carbobenzoxy-S-benzyl-L-cysteinyl-L-phenylalanyl-L-phenylalanylazide and 70 parts by volume of triethylamine in 500 parts by volume of dimethylformamide is added.
The mixture is allowed to stand for 2 days at 20°C, after which twice its volume of ethylacetate is added and the resultant precipitate then washed with warm methanol. There are obtained 45 parts by weight of Ncarbobenzoxy- S-benzyl-L-cysteinyl-L-phenylalanyl-L-phenylalanyl-L-glutaminyl- L-asparaginyl-S-benzyl-L-cysteinyl-L-prolyl-ε-N-p-toluenesulfonyl-L-lysylglycinamide; MP 222°C.
Preparation of L-Cysteinyl-L-Phenylalanyl-L-Phenylalanyl-L-Glutaminyl-LAsparaginyl- L-Cysteinyl-L-Prolyl-L-Lysyl-Glycinamide: Metallic potassium is stirred into a solution of 10 parts by weight of N-carbobenzoxy-S-benzyl-Lcysteinyl- L-phenylalanyl-L-phenylalanyl-L-glutaminyl-L-asparaginyl-S-benzyl-Lcysteinyl- L-prolyl-ε-N-p-toluenesulfonyl-L-lysyl-glycinamide in 2,500 parts of dry liquid ammonia at boiling temperature of the solution, until a stable blue coloration appears. After the addition of 1.8 parts by weight of ammonium chloride, the solution is evaporated to dryness. The residue of this evaporation contains the desired L-cysteinyl-L-phenylalanyl-L-phenylalanyl-L-glutaminyl-Lasparaginyl- L-cysteinyl-L-prolyl-L-lysyl-glycinamide
Preparation of Felypressin: The aforesaid residue, containing the L-cysteinyl-Lphenylalanyl- L-phenylalanyl-L-glutaminyl-L-asparaginyl-L-cysteinyl-L-prolyl-Llysyl- glycinamide, is dissolved in 20,000parts by volume of 0.01 normal acetic acid and is then oxidized by passing air into the solution at a pH of 6.5 to 8.0 for 1 hour. The solution, which contains Felypressin, is adjusted to a pH of 4.0 to 5.0, whereupon 100 parts by weight of sodium chloride are added and the mixture evaporated to dryness, yielding a dry powder of good stability. It can be stored, and yields a clear solution, e.g., in water or other appropriate solvent. The solution may be used directly or, if desired, after dilution with water or a sodium chloride solution

brand name

PLV-2 (Novartis).

Therapeutic Function

Vasoconstrictor

General Description

Felypressin, 2-L-phenylalanine-8-L-lysinevasopressin, has relatively low antidiuretic activity and littleoxytocic activity. It has considerable pressor (i.e., vasoconstrictor)activity, which differs from that of epinephrine (i.e.,following capillary constriction in the intestine it lowers thepressure in the vena portae, whereas epinephrine raises theportal pressure). Felypressin also causes increased renalblood flow in the cat, whereas epinephrine brings about afall in renal blood flow. Felypressin is five times more effectiveas a vasopressor than is lysine vasopressin and is recommendedin surgery to minimize blood flow, especially inobstetrics and gynecology.