Abstract
It has been suggested that sigma receptor antagonists may be useful as antipsychotic drugs. N, N-dipropyl-2-[4-methoxy-3-(2-phenylethoxy)phenyl]-ethylamine monohydrochloride (NE-100) is a novel compound with high affinity for the sigma receptor (IC50 = 4.16 nM), but low affinity (IC50 > 10,000 nM) for D1, D2, 5-HT1A, 5-HT2 and phencyclidine (PCP) receptors. The head-weaving behavior induced by either (+)SKF10047 or PCP was dose-dependently antagonized by NE-100 with oral ED50 at 0.27 and 0.12 mg/kg, respectively. NE-100 did not affect dopamine agonists-induced stereotyped behavior and/or hyperactivity. NE-100 failed to induce catalepsy in rats. These findings indicate that NE-100 may have antipsychotic activity without the liability of motor side effects typical of neuroleptics.
MeSH terms
-
Animals
-
Anisoles / metabolism
-
Anisoles / pharmacology*
-
Antipsychotic Agents / metabolism
-
Antipsychotic Agents / pharmacology*
-
Behavior, Animal / drug effects
-
Binding, Competitive
-
Catalepsy / chemically induced
-
Dopamine Agents / pharmacology
-
Drug Interactions
-
Locomotion / drug effects
-
Male
-
Phenazocine / analogs & derivatives
-
Phenazocine / pharmacology
-
Phencyclidine / pharmacology
-
Propylamines / metabolism
-
Propylamines / pharmacology*
-
Radioligand Assay
-
Rats
-
Rats, Inbred Strains
-
Rats, Wistar
-
Receptors, sigma / antagonists & inhibitors*
-
Stereotyped Behavior / drug effects
Substances
-
Anisoles
-
Antipsychotic Agents
-
Dopamine Agents
-
Propylamines
-
Receptors, sigma
-
N,N-dipropyl-2-(4-methoxy-3-(2-phenylethoxy)phenyl)ethylamine monohydrochloride
-
SK&F 10047
-
Phenazocine
-
Phencyclidine