Pharmacology in vivo of the phenylindan derivative, Lu 19-005, a new potent inhibitor of dopamine, noradrenaline and 5-hydroxytryptamine uptake in rat brain

Naunyn Schmiedebergs Arch Pharmacol. 1985 Apr;329(2):101-7. doi: 10.1007/BF00501197.

Abstract

Behavioural effects on dopaminergic transmission of a phenylindane derivative, Lu 19-005 [(+/-)-trans-3-(3,4-dichlorophenyl)-N-methyl-l-indanamine, HCI], with potent inhibitory effect on dopamine (DA), noradrenaline (NA) and serotonin (5-HT) uptake in rats and the effect on DA, NA and 5-HT activity in mice have been studied and compared with those of other known DA, NA and 5-HT uptake inhibitors with different selectivity ratios. Lu 19-005 induced stereotyped behaviour after parenteral and oral administration with a duration of action of more than 24 h. The stereotyped licking and biting induced by Lu 19-005 was antagonized by reserpine and cis(Z)-flupentixol, but not affected by prazosin, p-chlorophenylalanine and alpha-methyl-p-tyrosine pretreatments. Metergoline slightly facilitated the onset of stereotypy. Lower doses of Lu 19-005 induced ipsilateral circling in unilaterally 6-hydroxy-DA-lesioned rats. Finally, Lu 19-005 antagonized the catalepsy induced by perphenazine. In mice, Lu 19-005 potentiated the apomorphine-induced gnawing, reversed tetrabenazine-induced ptosis and potentiated the behavioural effects of 5-HTP within a similar dose range. The effects of Lu 19-005 were compared with those of other reference compounds. Nomifensine had qualitatively similar effects in rats although of much shorter duration. In mice, nomifensine selectively reversed tetrabenazine-induced ptosis. Weaker effects in all test models were found with bupropion, LR 5182 and GBR 13.069, compounds with inhibitory effect on DA and NA uptake. The DA-, NA- and 5-HT-uptake inhibitor diclofensine, however, had no effect in rats except in the 6-hydroxy-DA-circling test and had low potency in mice. The specific 5-HT- and NA-uptake inhibitors citalopram and talsupram, respectively, were ineffective in all rat models.(ABSTRACT TRUNCATED AT 250 WORDS)

MeSH terms

  • 5-Hydroxytryptophan / antagonists & inhibitors*
  • 5-Hydroxytryptophan / metabolism
  • 5-Hydroxytryptophan / pharmacology
  • Animals
  • Brain / metabolism*
  • Dopamine / metabolism*
  • Dopamine / pharmacology
  • Drug Synergism
  • Humans
  • In Vitro Techniques
  • Indans / pharmacology*
  • Indenes / pharmacology*
  • Male
  • Mice
  • Norepinephrine / antagonists & inhibitors*
  • Norepinephrine / metabolism
  • Norepinephrine / pharmacology
  • Rats
  • Rats, Inbred Strains
  • Stereotyped Behavior / drug effects
  • Synaptosomes / metabolism

Substances

  • Indans
  • Indenes
  • Lu 19005
  • 5-Hydroxytryptophan
  • Dopamine
  • Norepinephrine