Muscarinic agonists exhibit functional dopamine antagonism in unilaterally 6-OHDA lesioned rats.
(5R,6R) 6-(3-propylthio-1,2,5-thiadiazol-4-yl)-1-azabicyclo[3.2.1]oc tane (PTAC) is a selective muscarinic ligand with high affinity for central muscarinic receptors, agonist mode of action at the muscarinic M2 and M4 receptor subtypes and substantially less or no affinity for central dopamine receptors. In the present study PTAC, as well as the muscarinic agonists oxotremorine, RS86 and pilocarpine, inhibited dopamine D1 and D2 receptor agonist induced contralateral rotation in unilaterally 6-OHDA lesioned rats. The dose of SKF 38393 used to induce contralateral rotation also caused an intense Fos protein immunoreactivity in the rat dorsolateral striatum on the lesioned site which was inhibited by PTAC indicating that the inhibition of rotation by PTAC was not due to non-specific peripheral side effects.
Fink-Jensen
A
A
Health Care Discovery, Novo Nordisk A/S, Måløv, Denmark.
Kristensen
P
P
Shannon
H E
HE
Calligaro
D O
DO
Delapp
N W
NW
Whitesitt
C
C
Ward
J S
JS
Thomsen
C
C
Rasmusseen
T
T
Sheardown
M J
MJ
Jeppesen
L
L
Sauerberg
P
P
Bymaster
F P
FP
D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000494:pharmacology; D000818:Animals; D000906:Antibodies; D014150:Antipsychotic Agents / Q000494:pharmacology; D001923:Brain Chemistry / Q000187:drug effects; D001643:Bridged Bicyclo Compounds / Q000494:pharmacology; D002799:Cholinergic Fibers / Q000737:chemistry / Q000187:drug effects*; D004298:Dopamine / Q000502:physiology; D018491:Dopamine Agonists / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology*; D008297:Male; D018721:Muscarinic Agonists / Q000494:pharmacology*; D016627:Oxidopamine; D010095:Oxotremorine / Q000494:pharmacology*; D010277:Parasympathomimetics / Q000494:pharmacology; D010862:Pilocarpine / Q000494:pharmacology; D016760:Proto-Oncogene Proteins c-fos / Q000032:analysis / Q000276:immunology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013378:Substantia Nigra / Q000166:cytology / Q000378:metabolism; D013388:Succinimides / Q000494:pharmacology; D013565:Sympatholytics; D013830:Thiadiazoles / Q000494:pharmacology
C115974:6-(3-propylthio-1,2,5-thiadiazol-4-yl)-1-azabicyclo(3.2.1)octane; D000906:Antibodies; D014150:Antipsychotic Agents; D001643:Bridged Bicyclo Compounds; D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D018721:Muscarinic Agonists; D010277:Parasympathomimetics; D016760:Proto-Oncogene Proteins c-fos; D013388:Succinimides; D013565:Sympatholytics; D013830:Thiadiazoles; D010862:Pilocarpine; C001886:2-ethyl-8-methyl-2,8-diazaspiro(4,5)decane-1,3-dione; D010095:Oxotremorine; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D016627:Oxidopamine; D004298:Dopamine