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1. The pharmacology of a novel 5-HT4 receptor antagonist, SB 204070 has been evaluated in the guinea-pig isolated distal colon longitudinal muscle-myenteric plexus (LMMP). 2. SB 204070 is a highly potent antagonist of 5-HT-evoked cholinergically-mediated contractions in the guinea-pig distal colon. Low concentrations (10-100 pM) produced a shift to the right of the curve (apparent pA2 10.8 +/- 0.1) with no significant effect on the maximum response. With higher concentrations of SB 204070 (300 pM and above), the maximum response to 5-HT was reduced. 3. When tested against the partial 5-HT4 receptor agonist, BIMU 1, SB 204070 was active at similar low concentrations (10 pM and above) but produced a reduction in maximum, with no prior shift to the right of the curve, at all concentrations tested (10-300 pM). 4. The antagonism seen with SB 204070 is unlikely to be due to a non-selective effect since high concentrations (10 nM and 1 microM) of the compound had no effect on cholinergically-mediated contractions evoked by the nicotinic receptor agonist, DMPP, in the same preparation. SB 204070 is unlikely to be an irreversible antagonist since the effects of the compound could be reversed upon washing of the tissue. 5. Radioligand binding studies show that SB 204070 has a greater that 5000 fold selectivity for the 5-HT4 receptor over 5-HT1A, 5-HT1D, 5-HT1E, 5-HT2A, 5-HT2C, 5-HT3, GABAA, BDZ, TBPS, A1 adenosine receptors, alpha 1, alpha 2, beta 1, beta 2 adrenoceptors and D1, D2 and D3 dopamine receptors. 6. SB 204070 is a highly potent, highly selective 5-HT4 receptor antagonist and as such is an important new tool in evaluating the functional role of the 5-HT4 receptor.
K A Wardle, and
E S Ellis, and
G S Baxter, and
G A Kennett, and
L M Gaster, and
G J Sanger
September 1993,
British journal of pharmacology,
K A Wardle, and
E S Ellis, and
G S Baxter, and
G A Kennett, and
L M Gaster, and
G J Sanger
May 1994,
Naunyn-Schmiedeberg's archives of pharmacology,
K A Wardle, and
E S Ellis, and
G S Baxter, and
G A Kennett, and
L M Gaster, and
G J Sanger
December 1993,
British journal of pharmacology,
K A Wardle, and
E S Ellis, and
G S Baxter, and
G A Kennett, and
L M Gaster, and
G J Sanger
July 1995,
British journal of pharmacology,
K A Wardle, and
E S Ellis, and
G S Baxter, and
G A Kennett, and
L M Gaster, and
G J Sanger
October 1989,
Nihon Heikatsukin Gakkai zasshi,
K A Wardle, and
E S Ellis, and
G S Baxter, and
G A Kennett, and
L M Gaster, and
G J Sanger
November 1997,
Naunyn-Schmiedeberg's archives of pharmacology,
K A Wardle, and
E S Ellis, and
G S Baxter, and
G A Kennett, and
L M Gaster, and
G J Sanger
November 1996,
The American journal of physiology,
K A Wardle, and
E S Ellis, and
G S Baxter, and
G A Kennett, and
L M Gaster, and
G J Sanger
August 1991,
European journal of pharmacology,
K A Wardle, and
E S Ellis, and
G S Baxter, and
G A Kennett, and
L M Gaster, and
G J Sanger
May 2000,
European journal of pharmacology,
K A Wardle, and
E S Ellis, and
G S Baxter, and
G A Kennett, and
L M Gaster, and
G J Sanger
October 2017,
Neurogastroenterology and motility,
