Do imipramine and dihydroergosine possess two components--one stimulating 5-HT1 and the other inhibiting 5-HT2 receptors?

Abstract

The mechanisms by which imipramine and dihydroergosine stimulate the 5-HT syndrome in rats and inhibit the head-twitch response in rats and mice were studied. Imipramine- and dihydroergosine-induced stimulation of the 5-HT syndrome was inhibited stereoselectively by propranolol, a high affinity ligand for 5-HT1 receptor sites, but not by ritanserin, a specific 5-HT2 receptor antagonist. (-)-Propranolol potentiated the inhibitory effect of imipramine, but not of dihydroergosine on the head-twitch response, while ritanserin was without effect. Neither imipramine nor dihydroergosine were able to stimulate the 5-HT syndrome in the animals pretreated with p-chlorophenylalanine. As expected, 8-OH-DPAT, a selective 5-HT1A receptor agonist, stimulated, and 5-HT1B agonists CGS 12066B and 1-(trifluoromethylphenyl)piperazine (TFMPP) failed to stimulate the 5-HT syndrome induced in rats by pargyline and 5-HTP administration. A higher dose of ritanserin inhibited the syndrome. While 8-OH-DPAT alone produced all behavioral components of the 5-HT syndrome, dihydroergosine or imipramine alone even at very high doses never produced tremor or a more intensive forepaw padding as seen when these drugs were given in combination with pargyline and 5-HTP. A single administration of (-)-propranolol also inhibited the head-twitch response. This effect lasted in mice longer than after ritanserin administration. In in vitro experiments dihydroergosine expressed approximately twenty-fold higher affinity for 3H-ketanserin binding sites than imipramine. The results suggest that imipramine and dihydroergosine possess two components--one stimulating the 5-HT syndrome in rats by a presynaptic, presumably 5-HT1A-mediated mechanism, and the other inhibiting 5-HT2 binding sites.

• Authors: D Pericić, D Mück-Seler
• Journal: Life sciences (Life Sci) Vol. 46 Issue 19 Pg. 1331-42 ( 1990) ISSN: 0024-3205 [Print] Netherlands
• PMID: 2111865 (Publication Type: Journal Article)

Chemical References

• Ergotamines
• Piperidines
• Serotonin Antagonists
• Ritanserin
• 9,10-dihydroergosine
• Propranolol
• Imipramine

Topics

• Animals
• Brain (drug effects)
• Ergotamines (antagonists & inhibitors, pharmacology)
• Imipramine (antagonists & inhibitors, pharmacology)
• Male
• Mice
• Mice, Inbred CBA
• Motor Activity (drug effects)
• Piperidines (pharmacology)
• Propranolol (pharmacology)
• Radioligand Assay
• Rats
• Rats, Inbred Strains
• Ritanserin
• Serotonin Antagonists
• Syndrome