Substituted ergolines: potential antipsychotics with unique profile. I. Psychopharmacological characterization.
Different ergot structures (lumilysergol and lysergol) were chlorinated or brominated in the position 2, and the development of antidopaminergic activity was studied. The tested 2-halo-lysergols exerted neuroleptic-like action indicated by the suppression of conditioned avoidance response (CAR), and other effects characteristic of dopamine antagonists (cataleptogenic effect, prevention of amphetamine-induced toxicity, inhibition of L-DOPA-induced hyperactivity, lowering of spontaneous body temperature, antagonism of apomorphine-induced hypothermia). A second halogen substitution in the position 8 of the lysergol structure left the CAR suppression activity untouched, but abolished other dopamine antagonistic effects. This unique psychopharmacological profile refers to potential usefulness of the compounds in schizophrenia, and at the same time perhaps in particular forms of Parkinson's disease or tardive dyskinesia.
Groó
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Chemical Works of Gedeon Richter Ltd., Pharmacological Research Centre, Budapest, Hungary.
Palosi
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D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001058:Apomorphine / Q000494:pharmacology; D001362:Avoidance Learning / Q000187:drug effects; D001831:Body Temperature / Q000187:drug effects; D002375:Catalepsy / Q000139:chemically induced; D003913:Dextroamphetamine / Q000037:antagonists & inhibitors; D018492:Dopamine Antagonists; D004873:Ergolines / Q000494:pharmacology*; D007980:Levodopa / Q000494:pharmacology; D051379:Mice; D008815:Mice, Inbred Strains; D009043:Motor Activity / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains
D014150:Antipsychotic Agents; D018492:Dopamine Antagonists; D004873:Ergolines; D007980:Levodopa; C061885:lumelysergol; D001058:Apomorphine; C061884:lysergol; D003913:Dextroamphetamine