Inhibition of locus coeruleus neurons by the phencyclidine analog, N-[1-(2-benzo(b)thiophenyl)cyclohexyl]piperidine: evidence for potent indirect adrenoceptor agonist properties.
The effects of the phencyclidine derivative, N-[1-(2-benzo(b)thiophenyl)cyclohexyl]piperidine (BTCP), on the electrical activity of noradrenaline (NA) neurons of the locus coeruleus (LC) were studied in halothane-anesthetized rats. Systemic administration of BTCP potently inhibited LC neurons (ID50 of 1.1 +/- 0.1 mg/kg i.v.). This effect was mimicked by local microejection of BTCP into the LC. Both the systemic and local effects of BTCP were blocked by alpha 2-adrenoceptor antagonists and prevented by prior depletion of catecholamines with reserpine. These and other data suggest that BTCP behaves as a potent indirect NA agonist (i.e. via NA re-uptake and/or release systems).
Chergui
K
K
INSERM U 171, Hopital Sainte Eugénie, CHU Lyon-Sud, Pierre-Bénite, France.
Akaoka
H
H
Brunet
J L
JL
Charléty
P J
PJ
Saunier
C F
CF
Buda
M
M
Privat
A
A
Vignon
J
J
Kamenka
J M
JM
Chouvet
G
G
D000818:Animals; D004298:Dopamine / Q000378:metabolism; D008125:Locus Coeruleus / Q000187:drug effects*; D008297:Male; D009638:Norepinephrine / Q000378:metabolism; D010622:Phencyclidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011941:Receptors, Adrenergic / Q000187:drug effects*
D011941:Receptors, Adrenergic; C056415:1-(1-(2-benzo(b)thienyl)cyclohexyl)piperidine; D010622:Phencyclidine; D004298:Dopamine; D009638:Norepinephrine