Ro 11-2465 (cyan-imipramine), citalopram and their N-desmethyl metabolites: effects on the uptake of 5-hydroxytryptamine and noradrenaline in vivo and related pharmacological activities.

Abstract

Ro 11-2465 (cianopramine, cyan-imipramine) and citalopram (CIT), putative antidepressant drugs, are very potent and selective 5-hydroxytryptamine (5-HT) uptake inhibitors in vitro. This study investigated the effects of these drugs and their desmethyl metabolites, Ro 12-5419 (desmethylcianopramine, cyan-desipramine) and desmethylcitalopram (DCIT), respectively, on the uptake of 5-HT and noradrenaline (NA) in vivo [protection against H 77/77 (4, alpha-dimethyl-metatyramine)-induced displacement of 5-HT and NA] and on related pharmacological activities. All the investigated drugs antagonized H 77/77-induced displacement of 5-HT in the rat brain, though the effects of the metabolites were considerably weaker than those of the parent compounds. The H 77/77-induced displacement of brain NA in rats and mice was antagonized only by Ro 12-5419 and Ro 11-2465. All the drugs potentiated the pressor response to 5-HT in pithed rats; however, Ro 12-5419 and particularly Ro 11-2465 could also block the response when used in higher doses (greater than or equal to 0.1 mg/kg). Only Ro 12-5419 and Ro 11-2465 were able to potentiate the pressor response to NA. Ro 12-5419 also potentiated thyrotropin releasing hormone (TRH) hyperthermia and antagonized reserpine hypothermia in mice; Ro 11-2465 potentiated the TRH hyperthermia only. CIT and DCIT were inactive in both these tests. Of all the four drugs only CIT and Ro 12-5419 considerably stimulated the hind limb flexor reflex in spinal rats.(ABSTRACT TRUNCATED AT 250 WORDS)

• Authors: L Pawlowski, G Nowak, Z Górka, H Mazela
• Journal: Psychopharmacology (Psychopharmacology (Berl)) Vol. 86 Issue 1-2 Pg. 156-63 ( 1985) ISSN: 0033-3158 [Print] Germany
• PMID: 3927352 (Publication Type: Comparative Study, Journal Article)

Chemical References

• Antidepressive Agents
• Propylamines
• cianopramine
• Citalopram
• 4, alpha-dimethyl-3-tyramine
• Serotonin
• desmethylcitalopram
• Thyrotropin-Releasing Hormone
• Reserpine
• cyan-desipramine
• Imipramine
• Norepinephrine
• Tyramine

Topics

• Animals
• Antidepressive Agents (pharmacology)
• Brain (metabolism)
• Citalopram
• Drug Interactions
• Imipramine (analogs & derivatives, pharmacology)
• Male
• Mice
• Norepinephrine (metabolism)
• Propylamines (pharmacology)
• Rats
• Rats, Inbred Strains
• Reserpine (antagonists & inhibitors)
• Serotonin (metabolism)
• Thyrotropin-Releasing Hormone (pharmacology)
• Tyramine (analogs & derivatives, antagonists & inhibitors)