DuP 996 (3,3-bis(4-pyrindinylmethyl)-1-phenylindolin-2-one) enhances the stimulus-induced release of acetylcholine from rat brain in vitro and in vivo
✍ Scribed by Victor J. Nickolson; S. William Tam; Melvin J. Myers; Dr. Leonard Cook
- Publisher
- John Wiley and Sons
- Year
- 1990
- Tongue
- English
- Weight
- 963 KB
- Volume
- 19
- Category
- Article
- ISSN
- 0272-4391
No coin nor oath required. For personal study only.
✦ Synopsis
DuP 996, in micromolar concentrations, enhances the K'-stimulated release of acetylcholine (ACh) in rat cerebral cortex, hippocampus, and caudate nucleus slices in vitro, without effect on basal release. DuP 996 has very weak affinity for rat brain muscarinic or nicotinic receptors and does not inhibit acetylcholinesterase activity of rat brain. Upon subcutaneous administration, DuP 996, in doses of 0.1 to 1 mg/kg, increases the output of ACh from the cerebral cortex of awake, freely moving rats. In the mouse, scopolamine-induced hyperactivity is reduced by DuP 996 in doses of 0.3-0.5 mgikg (s.c.). In addition, pancuronium HBr-induced neuromuscular blockade is reversed by DuP 996 (ED50 = 1.7 mg/kg s.c.).
The enhancement by DuP 996 of K'stimulated transmitter release is not limited to the cholinergic system but is also observed in the dopaminergic system in the rat caudate nucleus and in serotonergic systems. K + -stimulated release of gamma-aminobutyric acid and glutamic acid in rat cerebral cortex, however, is only slightly enhanced by DuP 996, whereas no effects are observed on K+-stimulated release of cortical norepinephrine. DuP