Ketanserin-sensitive depressant actions of 5-HT receptor agonists in the neonatal rat spinal cord

British Journal of Pharmacology
N A ManuelH Crick

Abstract

1. The monosynaptic reflex (MSR), recorded in vitro from the neonatal rat spinal cord, was depressed by 5-hydroxytryptamine (5-HT), 5-carboxamidotryptamine (5-CT), methysergide and R(+)-8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT), and also by the selective 5-HT1D agonists, sumatriptan and N-methyl-3-(1-methyl-1-piperidinyl)-1H-indole-5-ethane sulphonamide (GR 85548). 2. Ketanserin (1 microM) and methiothepin (1 microM) reduced the duration of depressions elicited by 5-CT, but not those produced by 5-HT, sumatriptan, GR 85548, methysergide or 8-OH-DPAT. 3. The IC50 for MSR depression by 5-CT was 3.6, 2.1-6.2 nM (n = 4), by sumatriptan was 15.2, 12.9-18.0 nM (n = 32), by GR 85548 was 18.4, 11.7-29.1 nM (n = 12), by methysergide was 29.8, 10.2-87.1 nM (n = 4) and by 8-OH-DPAT was 0.21, 0.11-0.43 microM (n = 3) (geometric means and 95% confidence limits). 4. Ketanserin (0.1 or 1 microM) antagonized competitively responses to sumatriptan (apparent pA2 7.8 +/- 0.1, n = 5), GR 85548 (apparent pA2 7.6, unpaired data, n = 5), methysergide (apparent pA2 7.9 +/- 0.12, n = 4) and 8-OH-DPAT (apparent pA2 8.3 +/- 0.1, n = 3). Concentration-response curves to 5-CT showed a smaller, parallel shift to the right (apparent pA2 6.8 +/- 0.1...Continue Reading

References

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Citations

Dec 9, 2003·European Journal of Pharmacology·Motoko HondaHideki Ono
Oct 31, 1996·European Journal of Pharmacology·J M WatsonD N Middlemiss
Nov 15, 2002·Neuroscience Letters·Gonzalo HedoJose A Lopez-Garcia
Oct 17, 1998·British Journal of Pharmacology·J V SelkirkG W Price
Oct 22, 2004·European Journal of Pharmacology·Motoko HondaHideki Ono
Mar 31, 2006·European Journal of Pharmacology·Claire ScottJeannette Watson
May 29, 2014·Journal of Neural Transmission·Raffaele NardoneEugen Trinka
Sep 1, 1997·General Pharmacology·P J Pauwels

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