Scopolamine-induced cognitive impairment was used in healthy men to evaluate the central nervous system activity of the new cholinomimetic SDZ ENS-163. Eighteen subjects were treated in a crossover design with oral placebo/intravenous saline, 50 mg of oral SDZ ENS-163/intravenous saline, oral placebo/0.4 mg of intravenous scopolamine, and 50 mg of oral SDZ ENS-163/0.4 mg of intravenous scopolamine. The administration of placebo with scopolamine caused significant cognitive impairment, as assessed by the Computerized Neuropsychological Test Battery (CNTB), and also decreased salivation and heart rate. In contrast, SDZ ENS-163 with saline had no effect on CNTB scores, increased salivation, and increased heart rate. Despite the observed cholinomimetic effects of SDZ ENS-163 when administered with saline, the changes in CNTB scores, heart rate, and salivation were indistinguishable between placebo/scopolamine and SDZ ENS-163/scopolamine. Thus, 50 mg of oral SDZ ENS-163 has cholinomimetic activity in normal men, but this dose is insufficient to reverse the muscarinic effects of 0.4 mg of intravenous scopolamine.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1097/00004714-199502000-00009 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Pharmacological characterization of the muscarinic receptors mediating contraction of canine saphenous vein.
J Auton Pharmacol
December 1995
Institute of Pharmacology, Syntex Discovery Research, Palo Alto, CA 94304, USA.
1. The muscarinic receptor subtype mediating contraction of the canine saphenous vein has been characterized using a range of muscarinic agonists and subtype-selective antagonists. 2.
View Article and Find Full Text PDFEffects of the cholinomimetic SDZ ENS-163 on scopolamine-induced cognitive impairment in humans.
J Clin Psychopharmacol
February 1995
California Clinical Trials, Beverly Hills 90211, USA.
Scopolamine-induced cognitive impairment was used in healthy men to evaluate the central nervous system activity of the new cholinomimetic SDZ ENS-163. Eighteen subjects were treated in a crossover design with oral placebo/intravenous saline, 50 mg of oral SDZ ENS-163/intravenous saline, oral placebo/0.4 mg of intravenous scopolamine, and 50 mg of oral SDZ ENS-163/0.
View Article and Find Full Text PDFThe effect of oral dose volume on the absorption of a highly and a poorly water-soluble drug in the rat.
Biopharm Drug Dispos
July 1994
Department of Drug Metabolism, Sandoz Research Institute, East Hanover, NJ.
The influence of dose volume on drug absorption following oral administration of a highly and a poorly water soluble drug was examined in male Sprague-Dawley rats. A constant mass of each 14C-labeled compound was given via gavage in dose volumes of 1, 5, 10, and 20 mL kg-1. Blood levels, as well as the quantitative excretion of radioactivity, were measured following each treatment.
View Article and Find Full Text PDFEffects of muscarinic M2 and M3 receptor stimulation and antagonism on responses to isoprenaline of guinea-pig trachea in vitro.
Br J Pharmacol
May 1994
Syntex Discovery Research, Institute of Pharmacology R2-101, Palo Alto, CA 94303.
1. In guinea-pig and canine airway smooth muscle, there is reduced beta-adrenoceptor agonist sensitivity in tissues pre-contracted with muscarinic agonists when compared to tissues pre-contracted with other spasmogens, such as histamine or leukotriene D4. This reduced sensitivity may be the result of an interaction between muscarinic receptors and beta-adrenoceptors.
View Article and Find Full Text PDFThe thiolactone analogue of pilocarpine, SDZ ENS 163, acts in vitro and in vivo as a partial agonist at M1/M3 and as an antagonist at M2 muscarinic receptors. In vitro, the properties of SDZ ENS 163 have been investigated in several functional models for muscarinic receptors: it is a full agonist at M1 (rat superior cervical ganglion, carbachol = 100%) and a partial agonist at M3 receptors (guinea pig ileum). However, the drug shows antagonistic properties at M2 receptors (rat atria).
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!