BIMT 17, a 5-HT2A receptor antagonist and 5-HT1A receptor full agonist in rat cerebral cortex

  title={BIMT 17, a 5-HT2A receptor antagonist and 5-HT1A receptor full agonist in rat cerebral cortex},
  author={Franco Borsini and Ettore Giraldo and Eugenia Monferini and Giovanni Antonini and Marco Daniele Parenti and Giuseppe Bietti and Arturo Donetti},
  journal={Naunyn-Schmiedeberg's Archives of Pharmacology},
In the search for antidepressant agents with a rapid onset of action, we have found that compound BIMT 17 (1-[2-[4-(3-trifluoromethylphenyl)piperazin1-yl]ethyl]benzimidazol-[1H]-2-one) shows a good affinity for cerebral cortical 5-HT1A (pKi = 7.72) and 5-HT2A (pKi = 6.90) receptors, with no appreciable affinity for the other 5-HT receptor subtypes, including 5-HT2C. BIMT 17 reduced forskolin-stimulated cAMP accumulation in the cerebral cortex (pEC50 = 6.09) and in the hippocampus (pEC50 = 6.50… 

Trazodone and its active metabolite m-chlorophenylpiperazine as partial agonists at 5-HT1A receptors assessed by [35S]GTPγS binding

The agonist properties of trazodone and its active metabolite, m-chlorophenylpiperazine (m-CPP), at 5-HT1A receptors are elucidated by means of the guanosine-5′-O-(3-[ 35S]thio)-triphosphate ([35S]GTPγS) binding assay.

Region-dependent effects of flibanserin and buspirone on adenylyl cyclase activity in the human brain.

Findings suggest a region-related action of flibanserin and buspirone on forskolin-stimulated AC activity in human brain.

Pharmacology of flibanserin.

Flibanserin displays antidepressant-like activity in most animal models sensitive to antidepressants and does not display consistent effects in animal models of anxiety and seems to exert potential antipsychotic effects.

Flibanserin, a potential antidepressant drug, lowers 5‐HT and raises dopamine and noradrenaline in the rat prefrontal cortex dialysate: role of 5‐HT1A receptors

The results show that the stimulation of 5‐ HT1A receptors plays a major role in the effect of flibanserin on brain extracellular 5‐HT, DA and NA.

Studies on 1‐arylpiperazine derivatives with affinity for rat 5‐HT7 and 5‐HT1A receptors

Several 1‐aryl‐4‐(2‐arylethyl)piperazine derivatives were synthesized and tested in‐vitro for their binding affinity for 5‐HT7 and5‐HT1A receptors and behaved as partial agonist and full agonist, respectively, when tested for 5-HT7 receptor‐mediated relaxation of substance P‐induced guinea‐pig ileum contraction.

Retinal Neuroprotective Effects of Flibanserin, an FDA-Approved Dual Serotonin Receptor Agonist-Antagonist

Intraperitoneal delivery of flibanserin in a light-induced retinopathy mouse model provides retinal neuroprotection, and Mechanistic data suggests that this effect is mediated through 5-HT1A receptors and that flibanerin augments the expression of genes capable of reducing mitochondrial dysfunction and oxidative stress.



Tertatolol, a new beta-blocker, is a serotonin (5-hydroxytryptamine1A) receptor antagonist in rat brain.

It was found that (-)-tertatolol binds to 5- HT1 receptor subtypes in rat brain, particularly the 5-HT1A subtype in the hippocampus, and the binding of tertatoll to hippocampal 5-ht1A receptors was stereospecific.

Receptor reserve for 5-hydroxytryptamine1A-mediated inhibition of serotonin synthesis: possible relationship to anxiolytic properties of 5-hydroxytryptamine1A agonists.

The results suggest that 5- HT1A receptor-mediated regulation of 5-HT synthesis appears to be mediated by somatodendritic autoreceptors on5-HT neurons in the midbrain raphé nuclei, and suggest that these autoreceptor possess a large receptor reserve for agonists.

(−)Tertatolol is a potent antagonist at pre- and postsynaptic serotonin 5-HT1A receptors in the rat brain

The data indicate that (-)tertatolol is a potent competitive antagonist at both pre and post - and post (in the hippocampus) - synaptic 5-HT1A receptors in the rat brain.

Characterization of a novel 5-HT4 receptor antagonist of the azabicycloalkyl benzimidazolone class: DAU 6285

It is discovered that the benzimidazolone derivative DAU 6285, a search for 5-HT4 receptor antagonists, is 3–5 times more potent than tropisetron in blocking 5- HT, renzapride and BIMU 8 induced stimulation of adenylate cyclase activity in mouse embryo colliculi neurons.

Characterization of the 5-hydroxytryptamine1a receptor-mediated inhibition of forskolin-stimulated adenylate cyclase activity in guinea pig and rat hippocampal membranes.

  • M. De VivoS. Maayani
  • Biology, Chemistry
    The Journal of pharmacology and experimental therapeutics
  • 1986
The concentration-response data show that the inhibition of forskolin-stimulated adenylate cyclase activity in guinea pig and rat hippocampal membranes is mediated by a receptor with the characteristics of the 5-HT1A binding site, and it is proposed that this response is suitable for measuring activities and affinities of drugs acting at 5- HT1A receptors.

Differential coupling of 5-HT1A receptors occupied by 5-HT or 8-OH-DPAT to adenylyl cyclase

The classical pharmacological models do not exactly fit with characteristics of the negative coupling between transfected 5-HT1A receptors and adenylyl cyclase, and on membranes, the experimental procedures can modify this coupling differently depending on the nature of the agonist.

Lack of apparent receptor reserve at postsynaptic 5-hydroxytryptamine1A receptors negatively coupled to adenylyl cyclase activity in rat hippocampal membranes.

This was directly determined by examining the relationship between receptor occupancy and response at postsynaptic 5-HT1A receptors, in rat hippocampus, mediating the inhibition of forskolin-stimulated adenylyl cyclase activity, using the method of partial irreversible receptor inactivation.

Agonist/antagonist interactions with cloned human 5-HT1A receptors: variations in intrinsic activity studied in transfected HeLa cells

The present data show that EC50 values and intrinsic activity for a given drug are subject to large variations depending on the number of receptors expressed in the target tissue, and that intrinsic activity is not only ligand-dependent but also varies with the receptor-effector system studied.

S 14671: a naphtylpiperazine 5-hydroxytryptamine1A agonist of exceptional potency and high efficacy possessing antagonist activity at 5-hydroxytryptamine1C/2 receptors.

S 14671 is a structurally novel ligand manifesting high efficacy and exceptional potency at both pre- and postsynaptic 5-HT1A receptors, and is the most potent compound in every test.

5-HT1D receptors in guinea-pig and pigeon brain

It is suggested that 5-HT1D sites may be present in the brain of the majority of vertebrate species located higher than the sauropside-mammalian divergence in the phylogenic tree, whereas 5- HT1B sites are only found in some rodents.