Pentagastrin

Chemical Name N-carboxy-/3-alanyl-L-tryptophyl-L-methionyl-L-aspartylphenyl-L-alanin-amide N-tert-butyl ester 

Chemical Abstracts Registry No. 5534-95-2 Trade Name Manufacturer 

L-Tryptophanyl-L-methionyl-L-aspartyl-L-phenylalanine amide trifluoroacetate N-t-Butyloxycerbonyl- -alanine 2,4,5-trichlorophenyl ester 

A solution of 3.55 parts of L-trypTtophanyl-L-methionyl-L-aspartyl-L-phenylalanine amide trifluoroacetate in 30 parts of dimethylformamide is cooled to 0 C, and 1.01 parts of tri-ethylamine are added. The mixture is stirred while 1.84 parts of N-tert-butyloxycarbonyl-(3-alanine 2,4,5-trichlorophenyl ester are added at 0 C. The reaction mixture is kept at 0°C for 48 hours and then at 20°-23°C for 24 hours. The mixture is added to a mixture of 100 parts of ice-water, 0.37 part of concentrated hydrochloric acid (SG 1.18), 1.2 parts of acetic acid and 20 parts of ethyl acetate. The mixture is stirred for 15 minutes at 0°-10°C and is then filtered. The solid residue is washed with water and then with ethyl acetate, and is dried at 40°-50°C under reduced pressure. There is thus obtained N-tert-butyloxycarbonyl-)3-alanyl-L-tryptophanyl-L-methionyl-L-aspartyl-L-phenylalanine amide, MP 213°C with decomposition. 

---

N-tert-Butyloxyca rbony I- -a la nine-2,4,5-trichlorophenyl ester Pentagastrin 3-Butyl-1 -phenylamine Bufeniode 1 -Butyne... 

Salim (1992d) has performed several studies using reser-pine to produce a chronic model of peptic ulceration in rats. Administration of allopurinol, DMSO, cysteine or methionine-S-methylsulphonium chloride protected against injury. In addition allopurinol and DMSO were found to stimulate healing in this model. In an acute model of duodenal ulceration induced by pentagastrin and carbachol allopurinol, DMSO, cysteine or methionine-S-methylsulphonium chloride all protected against injury. 

Polypetides of medicinal interest were reviewed earlier in this series [453] and developments have continued apace. Angiotensinamide, pentagastrin, tetra-cosactrin and felypressin are now either widely used or growing in importance and serve to illustrate how rapidly this branch of medicinal chemistry is expanding. 

Gastric add secretion to pentagastrin H2 antagonists, proton pump inhibitors... 

Pharmacology Histamine H2 antagonists are reversible competitive blockers of histamine at the H2receptors. They also inhibit fasting and nocturnal secretions, and secretions stimulated by food, insulin, caffeine, pentagastrin, and betazole. 

Pentagastrin Silica gel G Analyte is examined by TLC in three different mobile phases 4-dimethyl -aminobenz -aldehyde in methanol/HCI The Rf of the analyte in three different mobile phases is determined and the colour of its spot is matched to that of the standard... 

Abelson JL, Le Melledo JM, Bichet DG (2001) Dose response of arginine vasopressin to the CCK-B agonist pentagastrin. Neuropsychopharmacology 24 161-169 Antoni FA (1993) Vasopressinergic control of pituitary adrenocortico tropin secretion comes of age. Front Neuroendocrinol 14 76-122... 

CCK8 concentrations were found to be lower in panic patients than in normal control subjects (Brambilla et al. 1993) and the CCK-B receptors were hyper-sensitive in panic disorders (Akiyoshi et al. 1996). Accordingly, CCK-B receptor agonists such as pentagastrin or CCK-4 have panic-like anxiogenic effects in humans (Radu et al. 2002). Clinical trials, however, have provided inconclusive data about the anxiolytic potential of CCK-B antagonists (Shlik et al. 1997). 

Radu D, Ahlin A, Svanborg P, Lindefors N (2002) Anxiogenic effects of the CCKB agonist pentagastrin in humans and dose-dependent increase in plasma C-peptide levels. Psychopharmacology (Berl) 161 396-403... 

Lesch KP, Wiesmann M, Hoh A (1992) 5-HTlA receptor-effector system responsivity in panic disorder. Psychopharmacology (Berl) 106 111-117 Levin AP, Doran AR, Liebowitz MR, Fyer AJ, Klein DF, Paul SM (1987) Pituitary adrenocortical unresponsiveness in lactate-induced panic. Psychiatry Res 21 23-32 Lines C, Challenor J, Traub M (1995) Cholecystokinin and anxiety in normal volunteers—an investigation of the anxiogenic properties of pentagastrin and reversal by the cholecystokinin receptor subtype-b-antagonist L-365,260. Br J Clin Pharmacol 39 235-242 Low K, Crestani F, Keist R, Benke D, Brunig I (2000) Molecular and neuronal substrate for the selective attenuation of anxiety. Science 290 131-134 Lucki I (1996) Serotonin receptor specificity in anxiety disorders. J Clin Psychiatry 57(Suppl 6) 5-10... 

Evidence of the involvement of CCK-B receptors in the neurobiology of anxiety has been strengthened by the findings that a closely related peptide, pentagastrin, produces dose-related and time-limited symptoms of social anxiety in both control subjects and patients with social phobia undergoing experimental social interactions (Uhde et al. 1993). Pentagastrin is a pentapeptide whose final tetrapeptide is identical to CCK-4. 

Histamine is released from mast cells in antigen-antibody reactions, as in anaphylaxis and allergy, which are the most widely known physiological reactions to histamine. However, these potentially fatal reactions are not caused by histamine alone. Other agents present in mast cells, such as serotonin, acetylcholine, bradykinin (a nonapeptide), and a slow-reacting substance or leukotriene (see chapter 8) also contribute. In the stomach, where histamine induces acid secretion, its release seems to be regulated by the peptide hormone pentagastrin. 

Van Vliet, I.M., Westenberg, H.G., Slaap, B.R., et ah Anxiogenic effects of pentagastrin in patients with social phobia and healthv controls. Biol. Psychiatry 4211), 76-78, 1997. 

On a weight basis 20 times more potent than cimetidine and 7.5 times more potent than ranitidine in inhibiting basal and pentagastrin stimulated gastric acid secretion. It is a competitive-noncompetitive inhibitor of receptors. It has a long-... 

In contrast, H3-selective histamine agonists inhibit acid secretion stimulated by food or pentagastrin in several species. 

DG = 2-deoxy-D-glucose Pgas = Pentagastrin BBS = bombesin, 4- = decrease 0 = no effect. 

---