Drugs online research references
Eur J Clin Pharmacol. 1989;37(5):507-12.
Application of a radioreceptor assay in a pharmacokinetic study of oxitropium bromide in healthy volunteers after single i.v., oral and inhalation doses.
Ensing K, de Zeeuw RA, in 't Hout WG, Cornelissen PJ.
University Centre for Pharmacy, Groningen, The Netherlands.
Oxitropium bromide (OXBR) is a new anticholinergic drug, which is expected to be useful in the treatment of nocturnal asthma. The only pharmacokinetic data were obtained with the 14C-labelled compound. A sensitive radioreceptor assay for the determination of unlabelled OXBR in plasma was developed, based on competition between OXBR and 3H-N-methylscopolamine for binding to muscarinic receptors. OXBR was isolated from plasma by ion-pair extraction and re-extraction. Active metabolites present in significant amounts might interfere in the assay, but this was not the case for OXBR metabolites. Detection limits were 300 pg.ml-1 and 3 ng.ml-1 for plasma and urine, respectively. For the latter no extraction step was required. The single dose pharmacokinetics of OXBR was studied following inhalation (3 mg), oral (2 mg) and i.v. (1 mg) administration to 12 men, following an open, cross-over design. After i.v. administration the kinetic parameters were: Vc 38.41; t1/2 alpha 5.3 min; t1/2 beta 142 min; AUC 8.9 h.ng.ml-1; renal excretion 50.2%, k10 3.5 l.h-1 and total clearance 1874 ml/min. The apparent bioavailabilities were 0.48% and 12.4% by the oral and inhalation routes, respectively, based on the cumulative renal excretion. There were moderate adverse reactions due to the anticholinergic properties of the drug.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2598990&dopt=Abstract
Brain Res. 1987 Aug 4;417(1):59-69.
Scopolamine-disruption of radial arm maze performance: modification by noradrenergic depletion.
Decker MW, Gallagher M.
Administration of muscarinic cholinergic antagonists impairs performance on a variety of memory tasks. We examined the hypothesis that denervation of norepinephrine input to the forebrain would augment this effect of cholinergic antagonists. Administration of 6-hydroxydopamine into the dorsal noradrenergic bundle did not by itself alter the performance of rats on a radial maze working memory task. In Experiment 1, scopolamine, a muscarinic antagonist, impaired the performance of the NE-depleted animals more than that of animals in an operated control group. This result was again observed in Experiment 2; but here a lesion by order of dose administration interaction provided evidence for recovery from the effects of NE-depletion. In Experiment 3, it was found that NE denervation did not alter the functional status of basal forebrain cholinergic neurons as reflected in in vitro determination of sodium-dependent, high affinity choline uptake in hippocampus and cortex. These results suggest that an age-related decline in brain NE neurons, as well as further deterioration in this system in some cases of Alzheimer's disease, may contribute to the cognitive and memory deficits more typically ascribed to cholinergic dysfunction.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3620979&dopt=Abstract
Neurochem Res. 1994 Apr;19(4):407-13.
Time course of decline of radiolabeled acetylcholine formed following intracerebroventricular administration of tritiated choline: effects of oxotremorine and scopolamine.
Bertrand N, Bralet J, Beley A.
Laboratoire de Pharmacodynamie, Faculte de Pharmacie, Dijon, France.
Rats were injected intracerebroventricularly with 5 microCi of [methyl-3H]choline. The time course of decline of the radiolabeled acetylcholine (ACh) formed was estimated in the ipsilateral cerebral cortex and striatum. The [3H]ACh levels declined biphasically from the cerebral tissue. The initial decline proceeded rapidly, after which labeled ACh declined more slowly. Scopolamine (1 mg/kg, i.v.) caused a significant increase in the rate of [3H]ACh disappearance, which can be interpreted as an enhancement of ACh release. By contrast, oxotremorine (0.8 mg/kg, i.v.) markedly reduced the [3H]ACh disappearance. The results show that drug-induced changes in cholinergic neuronal activities can be estimated from the disappearance of radioactive ACh after labeling the endogenous transmitter through intracerebroventricular administration of labeled choline.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8065497&dopt=Abstract
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