BRL 46470 potently antagonizes neural responses activated by 5-HT3 receptors

  title={BRL 46470 potently antagonizes neural responses activated by 5-HT3 receptors},
  author={Nigel R. Newberry and Clare J. Watkins and T S Sprosen and Thomas P Blackburn and David Grahame Grahame-Smith and Ronald A. Leslie},

Electrophysiological consequences of ligand binding to the desensitized 5‐HT3 receptor in mammalian NG108‐15 cells.

It is concluded that the high‐affinity binding of agonists to the desensitized form of the 5‐HT3 receptor is being studied, which is compatible with the cyclic model of receptor activation and desensitization.

Multiple 5‐HT receptors in the guinea‐pig superior cervical ganglion

5‐HT activates three pharmacologically distinct receptors to depolarize the guinea‐pig SCG, and it is believed that this response may be mediated by a novel receptor; but its pharmacology is closest to that of receptors in the 5‐HT2 receptor family.

Preclinical and clinical pharmacology of the 5-HT3 receptor antagonists

  • H. Wolf
  • Biology, Medicine
    Scandinavian journal of rheumatology. Supplement
  • 2000
Repeatedly demonstrated efficacy of 5-HT3-receptor antagonists in patients suffering from fibromyalgia raises the question for the mechanism of action involved, and possibly provides an approach for the causal explanation of favourable treatment results with 5- HT3- receptor antagonists with negligible affinity for other receptors.

Effect of ramosetron on short-circuit current response in rat colonic mucosa.

Prolonged anti‐emetic activity and 5‐HT3‐receptor antagonism by BRL 46470 in conscious ferrets

It is concluded that BRL 46470 has a potent and long-lasting ability to antagonize actions that are mediated by the 5-HT3 receptor in-vivo.

Modulation of the firing activity of noradrenergic neurones in the rat locus coeruleus by the 5‐hydroxtryptamine system

The data support the notion that the 5‐HT system tonically modulates NA neurotransmission since the lesion of 5‐ HT neurones enhanced the LC NA neurones firing activity and the suppressant effect of WAY 100635 on the firing activity ofNA neurones was abolished by this lesion.



Identification and distribution of 5-HT3 receptors in rat brain using radioligand binding

Direct evidence for the existence of 5-HT3 receptors in rat brain tissue and their distribution is reported, based on high affinity binding of the potent 5- HT3 receptor antagonist 3H-GR65630 to homogenates of rat entorhinal cortex.

Pharmacological characterization of 5‐hydroxytryptamine‐induced depolarization of the rat isolated vagus nerve

Five‐HT, PBG and 2‐methyl‐5‐HT had no demonstrable agonist effects at non‐5-HT receptors on the rat vagus nerve, and Tropacaine and m‐chlorophenylpiperazine were found to behave as reversible competitive antagonists of 5‐HT‐induced depolarization of thevagus nerve.

Effects of the 5‐HT3 receptor antagonist, GR38032F, on raised dopaminergic activity in the mesolimbic system of the rat and marmoset brain

It is concluded that the 5‐HT3 receptor antagonist GR38032F, and the neuroleptic agents fluphenazine, sulpiride and haloperidol, can reduce raised mesolimbic dopaminergic activity in the rat and marmoset.

Serotonin facilitates GABAergic transmission in the CA1 region of rat hippocampus in vitro.

The results suggest that serotonin directly excites GABAergic interneurones acting on a 5‐HT3 receptor and consequently increasing the frequency of inhibitory synaptic events recorded in CA1 pyramidal cells.