Is dopamine antagonism a requisite of neuroleptic activity?
Neuroleptic activity in laboratory animals is characterized by a decrease in locomotor activity, ptosis, catalepsy, antagonism of certain amphetamine-induced responses, and inhibition of a conditioned avoidance response. Neuroleptics have also been shown to be potent antagonists of dopamine (DA), cis-5,6-Dimethoxy-2-methyl-3-[2-(4-phenyl-1-piperazinyl)-ethyl]indoline (DHO) has been shown to possess the above described pharmacological profile. However, in contrast to known neuroleptics, DHO has no effect on DA levels, DA turnover rate or DA-stimulated cyclase; nor did it have an effect on tyrosine hydroxylase activity. In addition, DHO did not antagonize apomorphine-induced gnawing or amphetamine-induced stereotyped behavior, both of which have been reported to be DA-dependent. However, the agent decreased the level of norepinephrine in the forebrain. An attempt is made to demonstrate that the "DA-hypothesis" of schizophrenia may not be valid in all cases, and that the biochemistry of the disease state is very complex.
D000661:Amphetamine / Q000037:antagonists & inhibitors; D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001362:Avoidance Learning / Q000187:drug effects; D001763:Blepharoptosis / Q000139:chemically induced; D001923:Brain Chemistry / Q000187:drug effects; D002375:Catalepsy / Q000139:chemically induced; D018492:Dopamine Antagonists; D006801:Humans; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D051381:Rats; D012453:Saimiri; D013239:Stereotyped Behavior / Q000187:drug effects
D014150:Antipsychotic Agents; D018492:Dopamine Antagonists; D000661:Amphetamine