Atropine preparations

At this writing anticholinergic agents are not widely used for the symptomatic treatment of asthma, although compounds such as atropine [51 -55-8] C17H23NO3, (18) have been used for centuries (111). Inhalation of the smoke produced by burning herbal mixtures, such as Datura Stramonium provided bronchodilation and rehef from some of the symptoms of asthma. The major active component in these preparations was atropine or other closely related alkaloids (qv). 

The importance of tropinone as a possible starting-point for the production of the therapeutically valuable alkaloids atropine, hyoscyamine, cocaine, tropacocaine and the artificial tropeines (p. 73) led Robinson to consider the possibility of preparing this substance by a simple method. Starting with the idea that the formula for tropinone (XXX) may be regarded as made up of the formulae of the residues of succindialdehyde (XXVII), methylamine (XXV III) and acetone (XXIX), he found that a mixture of these substances in water, when allowed to stand for thirty minutes produced tropinone, which could be detected by means of its characteristic dipiperonylidene derivative (bright yellow needles, m.p. 214°). 

The synthesis of tropinone 14, a precursor of atropine and related compounds, is a classical example. In 1917 Robinson has prepared tropinone 14 by a Mannich reaction of succindialdehyde 11 and methylamine 12 with acetone 13 better yields of tropinone were obtained when he used the calcium salt of acetonedicar-boxylic acid instead of acetone. Modern variants are aimed at control of regio-and stereoselectivity of the Mannich reaction. ... 

Esters of tropine have a venerable place in medicinal chemistry. One such compound, cocaine, the object of some current interest, was the natural product lead which led eventually to most of today s local anesthetics. A distantly related analogue is prepared by reaction of tropine (132) with 3,5-dimethylbenzoyl chloride. This leads to an ester structurally related to another ]ii ominent natural product, atropine (133). The product, tropanaerin (134), is described as an iinti.serotonergic agent intended for antimigraine use [34]. 

Chibro-Atropine (Merck Sharp Dohme-Chibret) generics and numerous combination preparations GB Lomotil (Searle)-comb. 

A second assay which has been used extensively in the characterization of 5-HT3 receptors is the rabbit isolated heart. Both the sympathetic and parasympathetic inputs to the rabbit heart can be influenced by stimulation of 5-HT3 receptors this preparation is usually performed in the presence of atropine to block parasympathetic effects [12]. Under these conditions, 5-HT and other 5-HT3 receptor agonists exert positive effects on rate and contractile force. Selective 5-HT3 receptor antagonists such as MDL 72222 [6], ICS 205-930 [3] and ondansetron [7] block the agonist effects in a concentration-related manner. 

To administer such large doses, the authors had to have the atropine solutions prepared in a more concentrated form. The new injectable ampoules contained 50 mg per cc instead of the usual 2 or 5mg. These megadoses of atropine, and the claim that the resulting coma and delirium could be reversed by 4 mg of a dmg known to be ineffective in treating atropine toxicity, might have caused their reports to be r arded as balderdash by some readers. 

Sir Henry Dale noticed that the different esters of choline elicited responses in isolated organ preparations which were similar to those seen following the application of either of the natural substances muscarine (from poisonous toadstools) or nicotine. This led Dale to conclude that, in the appropriate organs, acetylcholine could act on either muscarinic or nicotinic receptors. Later it was found that the effects of muscarine and nicotine could be blocked by atropine and tubocurarine, respectively. Further studies showed that these receptors differed not only in their molecular structure but also in the ways in which they brought about their physiological responses once the receptor has been stimulated by an agonist. Thus nicotinic receptors were found to be linked directly to an ion channel and their activation always caused a rapid increase in cellular permeability to sodium and potassium ions. Conversely, the responses to muscarinic receptor stimulation were slower and involved the activation of a second messenger system which was linked to the receptor by G-proteins. 

Buscopan is a branded preparation containing hyoscine butylbromide, an antimuscarinic agent that reduces gastrointestinal motility. Antimuscarinic agents are contraindicated in cases of angle-closure glaucoma as they may aggrevate the condition. Hyoscine butylbromide is a quaternary ammonium compound, unlike atropine, which is a tertiary ammonium compound. 

In the rat, we observed a decrease of the spontaneous frequency of right atrial preparations and biphasic inotropic effects in left atrial preparations. Negative effects were not antagonized by atropine. The positive inotropic effect was modified very little by prior reserpinization or prior exposure to propranolol and phentolamine but was sensitive to Mn ions. On the other hand. 

Belladonna acts in the same way as atropine it is available as a tincture and in certain polycomponent preparations used for their biliary and intestinal antispasmodic action. Belladonna alkaloids show rapid absorption from the gastrointestinal tract. 

Solution 1 is prepared from exactly 5 ml of 0.4092% w/v atropine sulphate solution and exactly 1 ml of 2.134% w/v homatropine hydrobromide solution. The solution is basified and extracted, the solvent is removed and the residue is treated with 2 ml of BSA and then diluted to 50 ml with ethyl acetate. Solution 3 is prepared from exactly 2 ml of eyedrops and exactly 1 ml of 2.134% w/v homatropine hydrobromide solution. The solution is basified and extracted, the solvent is removed and the residue is treated with 2 ml of BSA and then diluted to 50 ml with ethyl acetate. 

Diphenoxylate Lomotil) is a meperidine derivative used as an antidiarrheal. It exhibits no morphinelike effects at low doses, but it produces mUd opioid effects, such as sedation, euphoria, and dependence, at higher doses. Its salts are highly insoluble in water, which reduces recreational use. Preparations often include atropine. 

Diphenoxylate (marketed in combination with atropine as Lomotil in the United States) is chemically related to both analgesic and anticholinergic compounds. It is as effective in the treatment of diarrhea as the opium derivatives, and at the doses usually employed, it has a low incidence of central opioid actions. Diphenoxylate is rapidly metabolized by ester hydrolysis to the biologically active metabolite difenoxylic acid. Lomotil is recommended as adjunctive therapy in the management of diarrhea. It is contraindicated in children under 2 years old and in patients with obstructive jaundice. Adverse reactions often caused by the atropine in the preparation include anorexia, nausea, pruritus, dizziness, and numbness of the extremities. 

In isolated heart preparation, acetylcholine reduces the cardiac rate and in the presence of atropine, it can stimulate the heart causing ventricular arrhythmias. 

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