Abstract |
The effect of a novel 5-HT3 receptor antagonist, BRL 46470, has been studied on two electrophysiological models for 5-HT3 receptors: grease-gap recordings from rat isolated vagus nerve and whole-cell patch-clamp recordings from mouse neuroblastoma-rat glioma NG108-15 cells. Its action on the rat vagus nerve was compared to that of four other 5-HT3 receptor antagonists. On the rat vagus, BRL 46470 reduced the maximum depolarizing response to 5-HT in a concentration-dependent manner with an IC50 of 0.3-1.0 nM, but the EC50 for 5-HT was not appreciably affected. This action was similar to that of granisetron and ICS 205-930, but differed from that of GR38032F and (+)- tubocurarine which produced clear rightward shifts of the concentration-response curve to 5-HT. The 5-HT-induced fast inward current of voltage-clamped NG108-15 cells was also antagonized by 1 nM BRL 46470 in an insurmountable manner. In contrast to (+)- tubocurarine, the action of BRL 46470 on the rat vagus nerve and NG108-15 cells did not readily reverse on washing with antagonist-free medium. It is concluded that BRL 46470 is a potent, insurmountable 5-HT3 receptor antagonist on the rat vagus and NG108-15 cells.
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Authors | N R Newberry, C J Watkins, T S Sprosen, T P Blackburn, D G Grahame-Smith, R A Leslie |
Journal | Neuropharmacology
(Neuropharmacology)
Vol. 32
Issue 8
Pg. 729-35
(Aug 1993)
ISSN: 0028-3908 [Print] England |
PMID | 8413836
(Publication Type: Journal Article)
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Chemical References |
- Bridged Bicyclo Compounds
- Bridged Bicyclo Compounds, Heterocyclic
- Indoles
- Serotonin Antagonists
- BRL 46470
- Ondansetron
- Tropisetron
- Tubocurarine
- Granisetron
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Topics |
- Animals
- Bridged Bicyclo Compounds
(pharmacology)
- Bridged Bicyclo Compounds, Heterocyclic
- Electrophysiology
- Glioma
(physiopathology)
- Granisetron
(pharmacology)
- In Vitro Techniques
- Indoles
(pharmacology)
- Kinetics
- Male
- Neuroblastoma
(physiopathology)
- Neurons
(drug effects)
- Ondansetron
(pharmacology)
- Rats
- Rats, Sprague-Dawley
- Serotonin Antagonists
(pharmacology)
- Tropisetron
- Tubocurarine
(pharmacology)
- Tumor Cells, Cultured
- Vagus Nerve
(drug effects)
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