General pharmacology of the putative cognition enhancer linopirdine

Arzneimittelforschung. 1995 Apr;45(4):456-9.

Abstract

The putative cognition enhancer linopirdine (3,3-bis(4-pyrindinylmethyl)-1-phenylindolin-2-one, CAS 105431-72-9) is supposed to act by enhancing the release of neurotransmitters, especially acetylcholine. The present study assessed the effects of a single administration of this compound on the central nervous system in eight different rat and mouse models (CNS general pharmacology). In each test performed, linopirdine was administered subcutaneously in doses of 3, 10, and 30 mg/kg. The compound did not affect traction ability and nociceptive responsiveness nor did it induce catalepsy. Linopirdine impaired motor coordination in the balance rod test. The compound showed a distinct proconvulsive action in the pentylenetetrazole threshold dose test and induced in the highest dose tested (30 mg/kg) lethal seizures in some mice. It increased the duration of hexobarbital-induced anaesthesia in mice. Rats treated with linopirdine showed ptosis, salivation, slight sedation, paw beating and slight hypothermia. These results support the hypothesis that linopirdine acts by elevating the release of different neurotransmitters such as acetylcholine and dopamine. The compound has a low potential to produce side effects at pharmacodynamic active doses.

MeSH terms

  • Animals
  • Behavior, Animal / drug effects
  • Body Temperature / drug effects
  • Catalepsy / chemically induced
  • Cognition / drug effects*
  • Convulsants / pharmacology
  • Hexobarbital / pharmacology
  • Indoles / pharmacology*
  • Male
  • Mice
  • Mice, Inbred Strains
  • Pain Measurement / drug effects
  • Pentylenetetrazole / pharmacology
  • Postural Balance / drug effects
  • Pyridines / pharmacology*
  • Rats
  • Rats, Wistar

Substances

  • Convulsants
  • Indoles
  • Pyridines
  • Hexobarbital
  • linopirdine
  • Pentylenetetrazole