Lack of involvement of haloperidol-sensitive sigma binding sites in modulation of dopamine neuronal activity and induction of dystonias by antipsychotic drugs.
The present studies evaluated previous suggestions that haloperidol-sensitive sigma binding sites are involved in the modulation of dopamine (DA) neuronal activity and in the induction of the dystonic effects of antipsychotic drugs. These issues were addressed by evaluating the effects of compounds that have differing affinities for sigma binding sites, on the firing activity of DA neurons in the substantia nigra in chloral hydrate-anesthetized rats and on the ability to induce extrapyramidal motor dysfunction in squirrel monkeys sensitized to the dystonic effects of haloperidol. The agents studied included haloperidol, DTG (1,3-di-o-tolylguanidine), (+)-pentazocine, (+)-SKF 10,047, BMY 14802, 8-OH-DPAT and sulpiride. There was no relationship between affinity for sigma binding sites and the ability to either alter DA neuronal activity or to induce extrapyramidal motor dysfunction.
Meltzer
L T
LT
Department of Pharmacology, Parke-Davis Pharmaceutical Research Division, Warner-Lambert Co., Ann Arbor, MI 48105.
Christoffersen
C L
CL
Serpa
K A
KA
Pugsley
T A
TA
Razmpour
A
A
Heffner
T G
TG
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001480:Basal Ganglia Diseases / Q000139:chemically induced / Q000503:physiopathology; D004298:Dopamine / Q000502:physiology*; D004421:Dystonia / Q000139:chemically induced / Q000503:physiopathology*; D004594:Electrophysiology; D006220:Haloperidol / Q000494:pharmacology*; D008297:Male; D009474:Neurons / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017480:Receptors, sigma / Q000187:drug effects*; D012453:Saimiri
D014150:Antipsychotic Agents; D017480:Receptors, sigma; D006220:Haloperidol; D004298:Dopamine