Dopamine receptor agonistic and antagonistic effects of 3-PPP enantiomers

Psychopharmacology (Berl). 1983;81(3):199-207. doi: 10.1007/BF00427262.

Abstract

The pharmacological profile of the enantiomers of the proposed selective dopamine (DA) autoreceptor agonist 3-PPP [3-(3-hydroxyphenyl)-N-n-propylpiperidine] has been studied. In vitro both enantiomers showed weak DA agonistic activity, and (--)-3-PPP some DA antagonistic effect on DA-stimulated adenylate cyclase activity. Both enantiomers in low doses had a similar profile in vivo: Inhibition of locomotor activity of mice and rats, induction of contralateral circling behaviour in 6-hydroxy-DA-lesioned rats and an emetic effect in dogs. At higher doses, differential effects of the enantiomers were found: (+)-3-PPP induced hyperactivity, weak stereotyped behaviour and ipsilateral circling in hemitransected rats. (--)-3-PPP had depressant effects in high doses, inhibited d-amphetamine-induced hyperactivity and d-amphetamine-, methylphenidate- and apomorphine-induced stereotyped licking/biting in rats and antagonized apomorphine-induced emesis in dogs. However, (+)-3-PPP also showed a weak antagonistic activity against d-amphetamine-induced hyperactivity and d-amphetamine- and apomorphine-induced stereotypy in rats and inhibited apomorphine-induced emesis in dogs. It is suggested that both enantiomers have significant effects on postsynaptic DA receptors in high doses: (--)-3-PPP with weak antagonistic activity in some test models and (+)-3-PPP with agonistic and antagonistic effect. Since these effects of (+)-3-PPP were of low intensity at high doses, (+)-3-PPP may be a partial DA agonist at postsynaptic receptors in high doses.(ABSTRACT TRUNCATED AT 250 WORDS)

MeSH terms

  • Adenylyl Cyclases / metabolism
  • Animals
  • Antiemetics
  • Antipsychotic Agents / pharmacology
  • Catalepsy / chemically induced
  • Dogs
  • Dopamine / metabolism
  • Female
  • Guinea Pigs
  • Humans
  • Male
  • Mice
  • Motor Activity / drug effects
  • Norepinephrine / metabolism
  • Piperidines / pharmacology*
  • Rabbits
  • Rats
  • Rats, Inbred Strains
  • Receptors, Adrenergic, alpha / metabolism
  • Receptors, Dopamine / drug effects*
  • Serotonin / metabolism
  • Stereoisomerism
  • Stereotyped Behavior / drug effects
  • Synaptosomes / metabolism

Substances

  • Antiemetics
  • Antipsychotic Agents
  • Piperidines
  • Receptors, Adrenergic, alpha
  • Receptors, Dopamine
  • Serotonin
  • preclamol
  • Adenylyl Cyclases
  • Dopamine
  • Norepinephrine