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Biomedical subjects

E E Essien

Publications and source records attributed to E E Essien.

29 records · Page 2Linked to original sources
PubMed1981

Actions of chloroquine and its N-oxidation metabolites on the rectus abdominis muscle of the toad (Bufo regularis).

Using the isolate rectus abdominis muscle preparation of the toad (Bufo regularis) the pharmacological actions of chloroquine, chloroquine-N-oxide and chloroquine N-di-oxide were investigated. On their own at concentrations ranging from 7.5 x 10(-5) -5 x 10(-3)M, the compounds induced contractures, chloroquine being the most active. At lower concentrations (5 x 10(-7) - 5 x 10(-5) M), chloroquine and its N-oxides enhanced acetylcholine-induced contractures whereas they depressed the carbachol-evoked contractures. At higher concentrations (5 x 10(-4) - 5 x 10(-3)M), chloroquine and its N-oxides inhibited both ACh- and carbachol-induced contractures. Analysis of the results obtained showed that the antagonism between ACh (or carbachol) and chloroquine (or its N-oxides) is non-competitive. At low concentrations chloroquine and its N-oxides (5 x 10(-7) - 5 x 10(-5)M) inhibited the potentiating action of neostigimine on ACh-induced contractures. From the results obtained in the study presented here, it is suggested that the antagonism of acetylcholine (or carbachol) by chloroquine and its N-oxidation metabolites on this muscle preparation may be at the cellular level. It is also suggested that the compounds examined may be acting as anticholinesterases (with chloroquine being the most active).

Acetylcholine↗
PubMed1975

Metabolism of phenothiazines: identification of N-oxygenated products by gas chromatography and mass spectrometry.

The solid inlet mass spectra of the N-oxide and N-oxide sulphoxide metabolites of promazine, chlorpromazine and methotrimeprazine have been determined at different temperatures and compared with the mass spectra of the main thermolytic product of the N-oxides and N-oxide sulphoxides obtained during combined gas chromatography-mass spectrometry. Diagnostic ions were produced by direct insertion of the compounds at ambient temperature into the mass spectrometer. These ions distinguish the N-oxides of arylalkyl tertiary amines from the N-oxygenated derivatives of primary and secondary arylalkylamines.

Chlorpromazine↗
PubMed1975

Synthesis and characteristics of the enantiomers of the cyclic metabonate of methadone.

2-Ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (II), a cyclic metabonate of methadone was synthesized from methadone (I) and methadone-N-oxide (III). M-Chloroperbenzoic acid was used to oxidatively demethylate I while sulphur dioxide reductively demethylated III to give II. The importance of these syntheses lies in the fact that there is no attack on the asymmetric carbon atom in I or III, thus providing direct methods of obtaining the optical isomers of II.

Chromatography, Gas↗
PubMed1975

The metabolism of chlorpromazine and promethazine to give new 'pink spots'.

1. The 'pink spots' observed in the in vivo and in vitro metabolism of chlorpromazine and promethazine were identified as N-oxidation products of 2-chlorophenothiazine and phenothizaine,, respectively. 2. Incubations of the latter two compounds with fortified hepatic fractions from rabbit and guinea-pig gave the corresponding hydroxylamines, the nitroxides which were purplish-pink and gave characteristic e.s.r. signals, and the N-hydroperoxides which were the major pink compounds and gave no e.s.r. signals. Each hydroxylamine was readily oxidized to an N-hydroperoxide in air and the latter readily reduced back in solution to the corresponding hydroxylamine by ascorbic acid. 3. The synthesis, chemical properties and the i.r., u.v., n.m.r., e.s.r., and mass spectra of the above compounds, their sulphoxides and phenothiazine-N-peroxides are reported.

Animals↗
PubMedDate not supplied

Pharmacokinetics of chloroquine: saliva and plasma levels relationship.

The use of saliva levels as an alternative to plasma levels in monitoring chloroquine therapy was studied in five healthy volunteers. Subjects took two (250 mg) tablets of chloroquine diphosphate (300 mg chloroquine base) with 200 ml of water. Saliva and blood samples were collected at intervals over 6 days. Plasma was separated from blood samples after centrifugation while saliva samples were centrifuged to remove mucoid sediments. Both the plasma and saliva samples were analysed for chloroquine by a combination of thin-layer chromatography and spectrophotometry. Regression analysis was used to determine the correlation between saliva and plasma chloroquine levels. A significant correlation (r = 0.97, p less than 0.05) was observed between saliva and plasma levels of chloroquine. The saliva: plasma concentrations ratio was found to be 0.53. From the saliva: plasma relationship, the extent of chloroquine binding to plasma proteins was estimated to be 47%. The Cmax and AUC0-6 day values obtained from saliva data was about half those from plasma, while the Tmax obtained from both fluids remained the same. The saliva clearance rate (Cls/F) of chloroquine was about twice the plasma clearance rate (Cl/F). (Cls/F: 0.46 +/- 0.051/day/kg; 0.27 +/- 0.021/day/kg). However, the predicted Cl/F (0.27 +/- 0.031/day/kg) from saliva data was in agreement with Cl/F from plasma data. This was also true of the volume of distribution. The collection of saliva for measuring chloroquine levels provides a painless, non-invasive alternative to plasma sampling, and it is useful in predicting chloroquine pharmacokinetics.

Adult↗
PubMedDate not supplied

Chloroquine disposition in hypersensitive and non-hypersensitive subjects and its significance in chloroquine-induced pruritus.

Twenty-one healthy Nigerian volunteers distributed into four groups participated in a study to determine the significance of chloroquine disposition in chloroquine-induced pruritus. It involved the administration of chloroquine with or without promethazine pre-administration to the subjects. Group I consisted of 8 chloroquine non-hypersensitive subjects receiving 2 tablets of chloroquine sulphate (300 mg base); Group II consisted of 5 chloroquine non-hypersensitive subjects receiving 2 tablets of chloroquine sulphate 30 minutes after 25 mg promethazine tablet pre-administration; Group III consisted of 5 chloroquine hypersensitive subjects treated as in Group II; Group IV consisted of 3 hypersensitive subjects treated as in Group I. Blood (5 ml) and urine samples were collected periodically for up to 6 days post-dose. The samples were analysed for chloroquine and some of its oxidation metabolites by a specific HPLC method. Probit plots of cumulative drug/metabolite ratios were done to determine if there is polymorphism in chloroquine metabolism. There was bimodality only in the distribution of chloroquine/monodesethylchloroquine ratios, suggesting polymorphism in the metabolic oxidation of chloroquine in these subjects. Higher levels of monodesethylchloroquine were obtained in Group IV subjects when compared with any of the other groups. The oral clearance rate, elimination half-life, and volume distribution at steady state of chloroquine in the study groups were not significantly different (P greater than 0.05). In the absence of promethazine there appears to be an extensive metabolism of chloroquine in hypersensitive individuals to produce monodesethylchloroquine which probably determines the degree of pruritus experienced by an individual.

Adult↗