Biochemical and electrophysiological studies of the psychotropic compound, amperozide.
Amperozide (AB Ferrosan, FG 5606), a new antiaggressive agent which exhibits a diverse preclinical profile of in vivo and in vitro activities, was examined to determine its acute effects on noradrenergic neurons of the locus coeruleus. The firing rates of all locus coeruleus neurons tested were increased by IV administration of amperozide. The amperozide-induced increase in locus coeruleus firing rate was similar in magnitude to that of an alpha-2 antagonist; however, amperozide was weaker than the alpha-2 antagonist yohimbine in reversing clonidine-induced inhibition of locus coeruleus neuronal activity and had weak affinity at the alpha-2 receptor (Ki = 3.5 microM). Biochemically, amperozide displayed the most significant in vitro affinity at serotonin-2 receptors (Ki = 26 nM) and had low affinities at all other receptors examined. These properties are discussed in the context of amperozide's activation of the locus coeruleus as a part of its hypothetical mechanism of antiaggressive action.
Haskins
J T
JT
Wyeth Laboratories, Incorporated, Division of Experimental Therapeutics, Philadelphia, PA 19101.
Muth
E A
EA
Andree
T H
TH
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D007275:Injections, Intravenous; D008125:Locus Coeruleus / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D008297:Male; D009433:Neural Inhibition / Q000187:drug effects; D009638:Norepinephrine / Q000378:metabolism; D010879:Piperazines / Q000008:administration & dosage* / Q000378:metabolism / Q000494:pharmacology; D011619:Psychotropic Drugs / Q000008:administration & dosage* / Q000378:metabolism / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D017981:Receptors, Neurotransmitter / Q000187:drug effects / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism
D010879:Piperazines; D011619:Psychotropic Drugs; D017981:Receptors, Neurotransmitter; C049058:amperozide; D012701:Serotonin; D009638:Norepinephrine