Hypoglycaemic activity

II.f.2.2. Sulphonylureas. These drugs stimulate pancreatic /3-cell insulin secretion, reduce serum glucagon levels, potentiate insulin action on target tissues, and improve /3-cell function. The sulphonylureas differ in their potency, extent of hepatic metabolism, hypoglycaemic activity of their metabolites, renal excretion, peak and duration of action, side effects and costs. 

Neef, H., P. Declercq, and G. Laeke-man. Hypoglycaemic activity of selected European plants. Phytother Res 1995 9(1) 45-48. 

Kiho, T., Yamane, A., Hui, J., Usi, S., and Ukai, S. 1996. Polysaccharides in fungi XXXVI. Hypoglycaemic activity of a polysaccharide (CS-F30) from the cultural mycelium of Cordyceps sinensis and its effect on glucose metabolism in mouse liver. Biol. Pharm. Bull. 19(2), 294-296. 

Disposition in the Body. Readily absorbed after oral administration and rapidly metabolised to (—)-l-hydroxyhexamide which has about 2.5 times the hypoglycaemic activity of the unchanged drug. Minor metabolites include 4 -rran5-hydroxyacetohexam-ide, 4 -rrfl 5-hydroxy-l-hydroxyhexamide and, to a lesser extent, the A -cis-, 3 -cis-, and 3 -trans-isomers. About 80% of a dose is excreted in the urine in 24 hours, mainly as metabolites. 

Disposition in the Body. Absorbed after oral administration. It is extensively metabolised by hydroxylation, A-oxidation, and oxidation to several inactive metabolites thep-carboxy metabolite, which accounts for about 1% of the plasma concentration, has no hypoglycaemic activity but has some antithrombotic... 

This review will concentrate on new agents or new data on older agents reported in the past 5 years, and is confined to compounds with reported hypoglycaemic activity in man and/or animal models of IDDM or NIDDM. The patent literature has been recently reviewed [6] and will not be covered here. Established agents (sulphonylureas, biguanides) have been the subject of recent reviews and the reader is referred to those [4, 7-12]. 

U-56324 (28), a nicotinic acid derivative, has hypoglycaemic activity in the 18-h fasted normal rat [173] and stimulates in vitro insulin secretion [174]. Study of the in vitro activity in membrane patches from cultured mouse pancreatic jff-cells revealed that it acts directly on ATP-sensitive potassium channels and probably has the same mechanism of action as sulphonylureas [174]. 

This section describes compounds developed as CNS agents for the treatment of obesity or depression for which independent hypoglycaemic activity has been observed. Whether or not this secondary effect is also centrally mediated is unclear. The first of these agents to be identified was fenfluramine (87), a serotonin agonist anorectic agent developed in the early 1960s. Its antidiabetic activity has been studied in animals and man and has been recently reviewed [384, 385]. 

Sezik E, Aslan M, Yesilada E, Ito S. Hypoglycaemic activity of Gentiana olivieri and isolation of the active constituent through bioassay-directed fractionation techniques. Life Sci 2005 76(ll) 1223-38. 

The hypoglycaemic activity of a plant drag may be brought about through one or combinations of two or more of these mechanisms. Some of these mechanisms are briefly described below,... 

A further example is provided by the antidiabetic agent tolbutamide (Fig. 7.30) which was developed from a sulfonamide structure. Most sulfonamides are used as antibacterial agents, but some proved unsatisfactory since they led to convulsions brought on by hypoglycaemia (low glucose levels in the blood). Structural alterations were made to eliminate the antibacterial activity and to enhance the hypoglycaemic activity and this led to tolbutamide. 

One of the most promising novel hypoglycaemic agents for treatment of NIDDM is ciglitazone (5-(4-(l-methylcyclohexylmethoxy)benzyl)thiazol-idine-2,4-dione) (5) [57-60]. It has effective hypoglycaemic activity in insulin-... 

Oleuropein and hydroxy-tyrosol, derived from oleuropein hydrolysis [46], possess several biological properties certainly mediated by their antioxidant and free radical-scavenging ability (antimicrobial, hypotensive, vasodilatator and hypoglycaemic activities) [47],... 

Reactions of Carboxy- and Cyano-thiophens.—/8-Thenoylacrylic acid reacted with pyrrole to give (109) in good yield. The solid-state photo-oligomerization of the 2-thienylacrylic acid derivative (110) has been investigated. Some amides between thiophen-2-carboxylic acid and anthranilic acids have been prepared, in connection with work on their hypoglycaemic activity. ... 

The pharmacokinetics of tolbutamide 250 mg daily for 4 days were not significantly changed in 7 healthy subjects when cimetidine 800 mg daily was added for a further 4 days. Other studies also found no pharmacokinetic interaction between tolbutamide and cimetidine, or between tolbutamide and ranitidine, and the hypoglycaemic activity of tolbutamide remained unaltered by cimetidine. ... 

Akhtar, M.S., M.A. Khan, and M.T. Malik. 2002. Hypoglycaemic activity of Alpinia galanga rhizome and its extracts in rabbits. Fitoterapia 73(7-8) 623-628. 

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