Oxyphencyclimine Research Articles

Method for evaluating spasmolytic activity of drugs on the bile duct

Abstract A method has been described for examining the spasmolytic activity of drugs on the bile duct of the guinea-pig in situ. The terminal bile duct was pulled away from its insertion into the duodenum and perfused with Tyrode solution containing either carbachol or barium chloride to produce spasm. Injected intravenously, atropine methonitrate, oxyphencyclimine hydrochloride, tropenziline bromide, phenetamine, papaverine hydrochloride or diprophylline were spasmolytic.

Selection and evaluation of anticholinergics for transdermal drug delivery

The receptor affinities of 18 anticholinergics, expressed as dissociation constants, were determined in order to select the most active compounds. Six drugs showed high affinities towards the muscarinic receptor ( K d<30 nM), and these compounds were selected as possible candidates for transdermal drug delivery because they can theoretically provide therapeutic plasma concentrations by dermal application on a limited area. From the six selected anticholinergics (atropine sulphate monohydrate, benztropine mesylate, dexetimide hydrochloride, oxyphencyclimine hydrochloride, scopolamine hydrobromide trihydrate, tropicamide), the physicochemical characteristics are described, together with atropine base. These characteristics may be useful to explain possible differences in permeation experiments. The chemical structures, molecular weights, and p K a values were available from the literature. The partition coefficients, and the solubility, pH and stability in the dosing and receptor solutions were experimentally determined.

Antimuscarinic effects of (R)- and (S)- oxyphencyclimine hydrochloride.

The (R)-(+)- and (S)-(-)-enantiomers of the anticholinergic compound, oxyphencyclimine, were synthesized from (R)-(-)- and (S)-(+)-2-cyclohexyl-2-hydroxy-2-phenylethanoic acid, respectively. The potencies of the enantiomers were compared using a cholinergic receptor binding assay. The (R)-(+)-enantiomer inhibited binding 29 times more potently than the (S)-(-)-enantiomer.

Analysis of some antispasmodic drugs: oxyphencyclimine and glycopyrronium bromide

Oxyphencyclimine hydrochloride (via its tertiary amine group) and glycopyrronium bromide (via its quaternary ammonium group) were analysed by two different colorimetric methods. The first method depends on the dye-salt formation method using tropeolin ooo as the anionic dye and 1,2-dichloroethane as solvent for the extraction of the formed ion pairs. The coloured ion pairs have maximum absorption at 483-486 nm. The second method is based on the use of citric acid-acetic anhydride reagent. The coloured complex has maximum absorption at 562-565 nm.

Solubility characteristics of weak bases and their hydrochloride salts in hydrochloric acid solutions.

The pH-solubility profiles of four basic drugs were studied at 37°. The solubility of papaverine hydrochloride in acetate buffer showed a typical pH-profile, which increased with decrease in pH. On the other hand, the pH-solubility profile of the hydrochloride in HCl-sodium acetate buffer was not as simple as that in acetate buffer, showing as solubility maximum at approximately 3.7. Similar pH-profiles of solubility were observed for trihexyphenidyl hydrochloride, isoxsuprine hydrochloride, and oxyphencyclimine hydrochloride. The decrease in the solubility of these drugs at more acidic pH values could be rationalized on the basis of the common ion effect. The dissolution behavior of the free bases and that of the hydrochloride salts of papaverine, trihexyphenidyl, and isoxsuprine were compared in dilute hydrochloric acid solutions, in the pH range from 1.0 to 1.8. It was confirmed that a much higher solution concentration and dissolution rate could be obtained using the free bases than from the hydrochloride salts in the pH range of the stomach (pH 1.0-1.2 for papaverine, and pH 1.2-1.4 for trihexyphenidyl and isoxsuprine) due to the common ion effect. It is suggested that salt formation does not always result in an enhancement of solubility characteristics.

Toxicologic investigation of oxyphencyclimine hydrochloride, a new anticholinergic agent

1. 1. The oral LD 50 of oxyphencyclimine in mice and rats was 860 mg/kg and 1370 mg/kg, respectively. 2. 2. Rats were fed rations containing 25, 50, 100, 200, and 400 mg % of oxyphencyclimine for six months. Growth rate was the only parameter employed that was adversely effected. This effect started with the 100-mg level and became progressively more severe at the higher levels. 3. 3. Daily doses of 3, 10, 30, and 100mg of oxyphencyclimine per kilogram of body weight were administered orally to dogs for six months. There were no deleterious effects from this prolonged administration, as evidenced by the absence of any abnormal hematologic, biochemical, or histologic findings.