RT Journal Article
SR Electronic
T1 Coadministration of cholinesterase inhibitors and idazoxan: effects of neurotransmitters in rat cortex in vivo.
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 230
OP 240
VO 273
IS 1
A1 G Cuadra
A1 E Giacobini
YR 1995
UL http://jpet.aspetjournals.org/content/273/1/230.abstract
AB Based on previous results indicating that cholinesterase inhibitors (ChEI) elicit a significant and simultaneous increase in acetylcholine (ACh) and norepinephrine (NE) levels, we studied whether the NE elevation could down-regulate ACh levels and possibly decrease the therapeutical effect of these drugs. A modified microdialysis technique without ChEI in the probe was used to study the putative interaction of these neurotransmitters in cerebral cortex of freely moving rats. We administered physostigmine (PHY) (0.03 mg/kg) and heptylphysostigmine (HEP) (2 mg/kg) subcutaneously to animals pretreated with idazoxan (IDA) (i.p. or in the probe), a selective alpha-2 antagonist. IDA (20 mg/kg i.p. and 10(-4) M in the probe) did not modify the basal release of ACh. On the other hand, NE and dopamine (DA) were increased after both types of administration. PHY administered to rats pretreated with IDA (systemically or locally) induced a similar increase in the ACh levels as demonstrated for PHY alone. Conversely, coadministration of HEP with IDA i.p. produced a more sustained effect on ACh cortical levels than did HEP alone. These data suggest that a combination of cholinergic-adrenergic drugs may improve the pharmacological effect of ChEI.