Prototype drug

Several obvious variants exist. Tolbutamide, the prototypic drug, has some anti arrhythmic activity by an unknown mechanism. his side effect has become the principal action with tosifen, which itself does not in turn significantly lower blood... 

The release behavior depends on both the choice of polymer and on the formulation procedure. The best results were obtained with injection-molded samples. For prototypical drugs like p-nitroaniline, the drug release pattern followed closely that of the polymer degradation over a period of 9 months for PCPP. The correlation between release and degradation was still maintained in the more hydrophilic PCPP-SA, 20 80, where both processes were completed in 2 weeks. Compression molding can also be used for these polymers, but the correlation between drug release and polymer degradation is not as... 

Amphetamine (53) is the prototype drug in this group. One significant objective of molecular manipulation in this group is to retain the appetite depressant activity without significant central stimulation. This is as yet unrealized. Some of the drugs prepared with this purpose in mind are discussed in this section. Reductive alkylation of the nitrogen... 

Certain prototypic drug substrates have been used to characterize enzyme activity in the human brain tissue. Amitriptyline, for example, was shown to be demethylated to nortriptyline by both rat and human... 

Nizatidine Nizatidine is N-[2-[[[2-[(dimethylamino)methyl]-4-thiazolyl]methyl] thio] ethyl]-2-nitro-l,l-ethenediamine (16.2.15). According to its chemical structure, nizatidine is somewhat of a hybrid structure of ranitidine and famotidine, in which a side chain of ranitidine and carrying heterocycle, 2-aminothiazol, are used. Likewise, its synthesis also is a specific combination of pathways used for making both prototype drugs. 2-(Dimethyl-aminomethyl)-4-hydroxymethylthiazol serves as the initial compound, from which the desired nizatidine (16.2.15) is synthesized by subsequent reaction with 2-mercaptoethy-lamine hydrochloride and then with iV-methyl-l-methythio-2-nitroethenamine [71,72]. 

A large number of (3-blockers are on the market in the United States. Of these, propranolol, a nonselective (3-antagonist, was the first to be introduced and is the prototypical drug with which the others are compared. Metoprolol was the hrst (3i-selective drug and timolol the hrst (3-blocker approved for ophthalmic use. 

Reserpine (Serpasil) is the prototypical drug interfering with norepinephrine storage. Reserpine lowers blood pressure by reducing norepinephrine concentrations in the noradrenergic nerves in such a way that less norepinephrine is released during neuron activation. Reserpine does not interfere with the release process per se as does guanethidine. 

Use design methods to identify and optimize a lead compound as a prototype drug. 

Preparation of the prototype drug departs from the phenylenediamine strategy used in all of the previous examples. Condensation of thiazolo nitrile (53-2) with aniline catalyzed by aluminum chloride affords the amidine addition product (53-3). This is then converted to its reactive A -chloro derivative (53-4) by reaction with sodium hypochlorite. Treatment of that intermediate with a base such as potassium hydroxide leads directly to the cyclization product and thus the benzimidazole thiabendazole (53-6) [56]. The reaction can be rationalized by invoking as the first step the abstraction of chloride to leave behind a nitrene species such as (53-5) this would then readily insert in the CH bond at the ortho position. 

The prototype drug in this class is chlorphenamine (chlorpheniramine) maleate. It is a very potent HI antagonist with only weak... 

The two prototypical drugs of this group are furosemide and ethacrynic acid. The structures of these diuretics are shown in Figure... 

The macrolides are a group of closely related compounds characterized by a macrocyclic lactone ring (usually containing 14 or 16 atoms) to which deoxy sugars are attached. The prototype drug, erythromycin, which consists of two sugar moieties attached to a 14-atom lactone ring, was obtained in 1952 from Streptomyces erythreus. Clarithromycin and azithromycin are semisynthetic derivatives of erythromycin. 

The rapid expansion in genomics data makes it inevitable that targets will be identified whose functions are so poorly understood that the most rapid and efficient way to establish their involvement in disease will be through the development of prototype drugs. New approaches to drug discovery that are able to integrate many different types of information are needed to seize this opportunity and drive an optimally efficient discovery process. 

Members of the group of natural, semisynthetic, or synthetic alkaloid compounds prepared from opium are referred to as opioids. This group includes natural compounds usually denoted opiates, such as morphine and codeine, and the synthetic and semi synthetic compounds such as oxycodone, buprenorphine, fentanyl, methadone, and tramadol. The pharmacological effects and pharmacokinetic parameters of these drugs share many common characteristics and are illustrated with the prototypic drug in this class, morphine. 

In discussing the pharmacology of narcotic analgesics, morphine is considered in greater detail as a prototype drug, and all the other compounds are compared with it. 

The pharmacology of drugs that antagonize catecholamines at a- and B-adrenoceptors is presented in Chapter 10 Adrenoceptor Antagonist Drugs. This chapter will concentrate on two prototypical drugs, propranolol and prazosin, primarily in relation to their use in treatment of hypertension. 

Tricyclic antidepressants—so called because of the characteristic three-ring nucleus—have been used clinically for four decades (Figure 30-1). They closely resemble the phenothiazines chemically and, to a lesser extent, pharmacologically. Like the latter drugs, they were first thought to be useful as antihistamines with sedative properties and later as antipsychotics. The discovery of their antidepressant properties was a fortuitous clinical observation. Imipramine and amitriptyline are the prototypical drugs of the class as mixed norepinephrine and serotonin uptake inhibitors though they also have several other properties. 

Fibric acid derivatives (aryloxyisobutyric acids) include the prototypic drug gemfibrozil. These types of drugs are used mainly to lower triglycerides and to increase HDL. A large placebo-controlled primary prevention trial in hypercholesterolemic men showed that patients treated with gemfibrozil had a statistically lower number of myocardial infarctions, but not of deaths from all causes. 

One of the earliest strategies for the management of hypertension was to alter sodium balance by restriction of salt in the diet. Pharmacological alteration of salt balance became practical in the 1950s with the development of the orally active thiazide diuretics. Hydrochlorothiazide is a prototypic drug. Thiazides and related diuretics make up the most frequently used class of antihypertensive agents in the United States. 

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