Pharmacological actions of SM-9018, a new neuroleptic drug with both potent 5-hydroxytryptamine2 and dopamine2 antagonistic actions

Jpn J Pharmacol. 1990 Jul;53(3):321-9. doi: 10.1254/jjp.53.321.

Abstract

Pharmacological studies were undertaken to clarify the profile of cis-2-(4-(4-(1,2-benzisothiazol-3-yl)-1-piperazinyl) butyl) hexahydro-1H-isoindole-1,3-(2H)-dione hydrochloride (SM-9018), a new neuroleptic drug. SM-9018 had very high binding affinities for both 5-hydroxytryptamine2 (5-HT2) and dopamine2 (D2) receptors, unlike many other neuroleptics. SM-9018 also strongly inhibited 5-HT2 receptor-mediated behavior such as tryptamine-induced clonic seizure and D2 receptor-mediated behavior such as methamphetamine-induced hyperactivity, apomorphine-induced stereotypy and climbing behavior. SM-9018 possessed only a weak cataleptogenic activity, which may be clinically related to extrapyramidal side effects, despite its potent D2 antagonistic activity. Moreover, SM-9018 induced weak central depressant effects such as inhibition of spontaneous locomotor activity and motor coordination, as compared with classical neuroleptics (haloperidol and chlorpromazine). These results suggest that SM-9018 is a new neuroleptic drug with both potent 5-HT2 and D2 antagonistic activities and with low cataleptogenic and central depressant activities.

MeSH terms

  • Animals
  • Antipsychotic Agents / pharmacology*
  • Behavior, Animal / drug effects
  • Brain Chemistry / drug effects
  • Catalepsy / chemically induced
  • Dopamine Antagonists*
  • Indoles / pharmacology*
  • Isoindoles
  • Ketanserin / metabolism
  • Male
  • Methamphetamine / antagonists & inhibitors
  • Mice
  • Mice, Inbred Strains
  • Motor Activity / drug effects
  • Norepinephrine / antagonists & inhibitors
  • Norepinephrine / toxicity
  • Parasympatholytics
  • Psychomotor Performance / drug effects
  • Rats
  • Rats, Inbred Strains
  • Serotonin Antagonists*
  • Spiperone / metabolism
  • Stereotyped Behavior / drug effects
  • Thiazoles / pharmacology*

Substances

  • Antipsychotic Agents
  • Dopamine Antagonists
  • Indoles
  • Isoindoles
  • Parasympatholytics
  • Serotonin Antagonists
  • Thiazoles
  • Methamphetamine
  • Spiperone
  • Ketanserin
  • perospirone
  • Norepinephrine