Human Urinary Excretion of Orally Administered Anisotropine Methylbromide

Pfeffer, Morris; Schor, Joseph M.; Gluck, Norman; Semmel, Martin G.; Griboff, Solomon I.

doi:10.1002/jps.2600570107

Cited by 10 publications

(3 citation statements)

References 7 publications

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“…In addition to inhibiting microsomal drug oxidations, SKF 525-A has been shown to inhibit glucuronyl transferase (24,25,99,100) and mono amine oxidase (101,102) . No inhibition of acetylcholinesterase was ob served (101 ).…”

Section: Complex Patterns Of Inhibition Have Been Observed By Other Amentioning

confidence: 99%

Enhancement and Inhibition of Drug Metabolism

Anders¹

1971

Annu. Rev. Pharmacol.

141

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A large number of factors can alter rates of drug metabolism. This re view wiII discuss the enhancement and inhibition of drug metabolism. By enhancement is meant that increase in rate of in vitro drug metabolism ob served following the inclusion of other drugs or chemicals in the reaction mixture. This term should be distinguished from the enzyme induction re sulting from treatment of the intact animal with other drugs or hydrocar bons. Inhibition of drug metabolism, as used in this review, refers to the blockage of metabolism of one drug by another at the enzymic site. This restriction excludes those agents that reduce rates of drug metabolism by mechanisms other than competition at enzymic sites, such as treatment with carbon tetrachloride (1), morphine (2), thyroxine (3) , and others. In addi tion, the review wiII be restricted to hepatic microsomal mixed function oxi dases; enhancement and inhibition of hydrolytic, reductive, and conjugative pathways will not be considered. ENHANCEMENT OF DRUG METABOLISMEthyl isocyanide.-Imai & Sato (4, 5) reported that EtNC exerts both stimulatory and inhibitory effects on microsomal aniline hydroxylation. The inhibitory effect of EtNC was attributed to a direct competition between oxygen and EtNC. The mechanism of the stimulatory effect appeared to be more complicated. The EtNC concentration producing maximal enhance ment was a function of the aniline concentration; as the aniline concentra tion was increased, more EtNC was needed to produce maximal enhance ment suggesting that hoth compounds were com peting for the same enzyme system. In addition, s pecies differences were observed in the activation of aniline hydroxylation by EtNC. The largest degree of enhancement was ob ta ined in the rabbit; in contrast, EtNC produced only inhibition of aniline

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Section: Complex Patterns Of Inhibition Have Been Observed By Other Amentioning

confidence: 99%

Enhancement and Inhibition of Drug Metabolism

Anders¹

1971

Annu. Rev. Pharmacol.

141

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“…In reference to this point, Pentikainen, et al showed that a considerable amount of radioactivity was incorporated in the gastrointestinal wall after the oral administration of "C-hyoscine-N-butylbromide, a quaternary ammonium compound, so that a local anti-acetylcholine effect can be expected (7). Furthermore, It is generally recognized that anticholinergic quaternary ammonium compounds are poorly absorbed from the gastrointestinal tract (9)(10)(11)(12)(13)(14)(15). In the present study with cats, how ever, approx.…”

Section: Discussionmentioning

confidence: 99%

Relationship Between Pharmacological Activity and Blood Level of a New Anticholinergic Agent, Timepidium Bromide (Sa-504), in Cats

Tamaki¹,

Meshi

1976

Japanese Journal of Pharmacology

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Abstract-Relationship between pharmacological activities and blood levels of a new anticholinergic agent . as well as excretion, and distribution in the gastro intestinal tract were investigated in cats. The time courses of inhibitory effect of SA-504 on gastric motility were closely related to those of blood levels of SA-504 after intra gastric administration of 3H-labelled compound. Effects of SA-504 on the pupil of the eye, heart rate and blood pressure were much less than its inhibitory effects on gastric motility. The contents of 3H-SA-504 in the gastric wall were extremely high as compared with those in the blood and heart. About 23 % of the radioactivity ad ministered orally as 3H-SA-504 was excreted into the bile and 20% into the urine during a 24 hour period, suggesting that more than 4000 of the dose is absorbed from the alimentary tract of cats within 24 hours.Timepidium bromide (SA-504) is a potent spasmolytic agent with a low potency of side effects, such as mydriasis and dry mouth (1, 2). It is well known that, in general, anti cholinergic quaternary ammonium compounds are not well absorbed from the gastrointes tinal tract. However, it has been demonstrated that SA-504, a quaternary ammonium drug, produced clear inhibition on the gastric motility of cats when administered into the stomach, although the inhibitory action is obviously weaker than that after i.v. injection (3). This suggests that a sufficient amount of the drug for reducing the gastric motility is absorbed through the gastrointestinal tract of cats. To confirm the above assumption, relationship between blood levels and pharmacological activities of 3H-SA-504 was studied in cats. The intestinal absorption of 3H-SA-504 estimated by measuring biliary and urinary excretion of radioactivity, and distribution in the gastrointestinal tract were also investigated. MATERIALS AND METHODS Synthesis of 3H-SA-504The synthesis of 3H-SA-504 was carried out by the catalytic hydrogenation of brominated SA-504 with '3H,' gas, as shown in Fig. 1. Brominated SA-504 (100 mg) was dissolved in 2 ml of 3 °0 KOH-MeOH and hydrogenated in the presence of palladium black (10 mg). The specific activity of the product was 100 ,,iCi/nig and the radiochemical purity was more than 98 % as determined by thin-layer chromatography (TLC).

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“…It was noted in these studies that the excretion of sulfonamides was markedly influenced by urinary pH ; the more basic, the more rapid the sulfonamide excretion. Other drugs whose urinary excretion was investigated were phenformin, p-butoxyphenylacethydroxamic acid, anisotropine, and urea (1380)(1381)(1382)(1383)(1384). The excretion and metabolism of pheniramine, brompheniramine, amphetamine, phenobarbital, and metopimazine were the subject of various articles (1374)(1375)(1376)(1377)(1378)(1379).…”

Section: Bioph Arm Aceuticsmentioning

confidence: 99%