Long-acting

Colourless prisms m.p. 49-50 C, b.p. 184 C. Prepared by the action of ammonia on ethyl chloroformate. Used as a long-acting anaesthetic for laboratory animals. 

The use of SPPS allows synthesis of both native oligopeptides and important synthetic analogues. Many of these fragments or substituted analogues have been found to be equal to, or more potent than, the parent molecule and to exhibit long-acting and antagonistic activities. 

Human Extended Insulin Zinc Suspension. Ultralente Humulin U is a long-acting form of human insulin produced by recombinant DNA techniques. It is adrninistered subcutaneously and should not be given intravenously. The time course of this preparation is similar for onset of activity but shorter for maximum activity and duration of action compared with ultralente preparations of animal origin. Insulins of the lente series can be mixed in any proportion to obtain the desired dose and modified activity. 

Galanthamine (23) is an alkaloid extracted from the common snowdrop Galanthus nivalis. This compound is a long-acting, competitive AChE inhibitor which appears to be somewhat more specific for acetylcholinesterase than plasma butyrylcholinesterase (132). It is well tolerated during long-term treatment (133) and is being evaluated clinically for AD (134). 

Bopindolol is a long-acting, nonselective P-adrenoceptor blocker. It has mild membrane stabilizing activity and ISA. In vivo, the compound is hydrolyzed to its active metabohte. Because of this prodmg feature the onset of action is slower than other available P-adrenoceptor blockers. Preliminary pharmacokinetic studies indicate that the compound is weU absorbed, is 70% bioavailable, and peak plasma levels are achieved in about 2 h. Whereas its elimination half-life is 4—8 h, P-adrenoceptor blocking action (- 40%) is stiU apparent after 48 h. The dmg is being studied in hypertension, angina, and arrhythmias (43). 

Bisoprolol fumarate is a long-acting, cardioselective -adrenoceptor blocker, and is the most potent cardioselective -adrenoceptor blocker available. Bisoprolol has no ISA. At high concentrations it has membrane-stabilizing activity. The dmg has a "balanced clearance", ie, half is excreted by the kidneys and half is eliminated by the Hver and its excretion is not affected by functional impairment of either organ. It is approved in Europe for hypertension and is being studied in angina (43). 

Bevantolol hydrochloride is a moderately lipophilic, long-acting, cardioselective -adrenoceptor blocker. It has no ISA but has membrane-stabilizing activity. The dmg is in use in Europe for the treatment of hypertension and angina. It is rapidly absorbed from the GI tract. Peak plasma levels occur in 1—2 h. It is metabolized extensively in the Hver to a metaboHte that has some ISA. It is excreted by the Hver and the kidneys and excretion is delayed in patients having kidney failure. 

The currendy (ca 1992) marketed injectable and implantable contraceptives are designed to be effective for maximum periods of three months and five years, respectively. There is Htde evidence from programmatic or health reasons that an injectable formulation with a longer effective life span, eg, six months, would not be equally effective. The acceptabiUty and effectiveness of long-acting contraceptives may be determined by the means by which a community deUvers contraceptive products to the pubHc the active life of a product may be determined by economic rather than programmatic or health related factors. 

Long-acting activity of injectable contraceptives can be accompHshed via a number of different approaches. Steroid activity can be extended over a... 

Long-acting progestins act primarily as ovulation inhibitors. An important secondary component is their effect on the cervical mucus and endometrium, achieved at circulating blood dmg levels below those required for ovulation inhibition (40). 

Antimicrobial spectrum, pharmacodynamic and phamacokinetic characteristics of rifabutin, a long-acting antituberculosis semisynthetic antibiotic of rifam-icin group 99MI13. 

Finally, attachment of a rather complex side chain to the para position of the benzene ring on the sulfonamide leads to the very potent, long-acting oral antidiabetic agent, glyburide (215). Preparation of this compound starts with the chlorosul-fonation of the acetamide of 3-phenethylamine (209). The resulting sulfonyl chloride (210) is then converted to the sulfonamide (211) and deacylated (212). Reaction with the salicylic acid derivative, 213, in the presence of carbodiimide affords the amide, 214. Condensation of that with cyclohexylisocyanate affords glyburide (215). ... 

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