PMID- 10193663
OWN - NLM
STAT- MEDLINE
DCOM- 19990601
LR  - 20220321
IS  - 0014-2999 (Print)
IS  - 0014-2999 (Linking)
VI  - 368
IP  - 2-3
DP  - 1999 Mar 5
TI  - Characterisation of the 5-HT receptor binding profile of eletriptan and kinetics 
      of [3H]eletriptan binding at human 5-HT1B and 5-HT1D receptors.
PG  - 259-68
AB  - The affinity of eletriptan 
      ((R)-3-(1-methyl-2-pyrrolidinylmethyl)-5-[2-(phenylsulphonyl )ethyl]-1H-indole) 
      for a range of 5-HT receptors was compared to values obtained for other 5-HT1B/1D 
      receptor agonists known to be effective in the treatment of migraine. Eletriptan, 
      like sumatriptan, zolmitriptan, naratriptan and rizatriptan had highest affinity 
      for the human 5-HT1B, 5-HT1D and putative 5-ht1f receptor. Kinetic studies 
      comparing the binding of [3H]eletriptan and [3H]sumatriptan to the human 
      recombinant 5-HT1B and 5-HT1D receptors expressed in HeLa cells revealed that 
      both radioligands bound with high specificity (>90%) and reached equilibrium 
      within 10-15 min. However, [3H]eletriptan had over 6-fold higher affinity than 
      [3H]sumatriptan at the 5-HT1D receptor (K(D)): 0.92 and 6.58 nM, respectively) 
      and over 3-fold higher affinity than [3H]sumatriptan at the 5-HT1B receptor 
      (K(D): 3.14 and 11.07 nM, respectively). Association and dissociation rates for 
      both radioligands could only be accurately determined at the 5-HT1D receptor and 
      then only at 4 degrees C. At this temperature, [3H]eletriptan had a significantly 
      (P<0.05) faster association rate (K(on) 0.249 min(-1) nM(-1)) than 
      [3H]sumatriptan (K(on) 0.024 min(-1) nM(-1)) and a significantly (P<0.05) slower 
      off-rate (K(off) 0.027 min(-1) compared to 0.037 min(-1) for [3H]sumatriptan). 
      These data indicate that eletriptan is a potent ligand at the human 5-HT1B, 
      5-HT1D, and 5-ht1f receptors and are consistent with its potent vasoconstrictor 
      activity and use as a drug for the acute treatment of migraine headache.
FAU - Napier, C
AU  - Napier C
AD  - Department of Discovery Biology, Pfizer Central Research, Sandwich, Kent, UK.
FAU - Stewart, M
AU  - Stewart M
FAU - Melrose, H
AU  - Melrose H
FAU - Hopkins, B
AU  - Hopkins B
FAU - McHarg, A
AU  - McHarg A
FAU - Wallis, R
AU  - Wallis R
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PL  - Netherlands
TA  - Eur J Pharmacol
JT  - European journal of pharmacology
JID - 1254354
RN  - 0 (HTR1B protein, human)
RN  - 0 (Indoles)
RN  - 0 (Oxazoles)
RN  - 0 (Oxazolidinones)
RN  - 0 (Piperidines)
RN  - 0 (Pyrrolidines)
RN  - 0 (Receptor, Serotonin, 5-HT1B)
RN  - 0 (Receptor, Serotonin, 5-HT1D)
RN  - 0 (Receptors, Serotonin)
RN  - 0 (Triazoles)
RN  - 0 (Tryptamines)
RN  - 10028-17-8 (Tritium)
RN  - 22QOO9B8KI (eletriptan)
RN  - 2FS66TH3YW (zolmitriptan)
RN  - 51086HBW8G (rizatriptan)
RN  - 8R78F6L9VO (Sumatriptan)
RN  - QX3KXL1ZA2 (naratriptan)
SB  - IM
MH  - Animals
MH  - Binding, Competitive
MH  - COS Cells
MH  - Cell Line
MH  - Cold Temperature
MH  - HeLa Cells
MH  - Humans
MH  - Indoles/*metabolism
MH  - Kinetics
MH  - Oxazoles/metabolism
MH  - *Oxazolidinones
MH  - Piperidines/metabolism
MH  - Pyrrolidines/*metabolism
MH  - Radioligand Assay
MH  - Receptor, Serotonin, 5-HT1B
MH  - Receptor, Serotonin, 5-HT1D
MH  - Receptors, Serotonin/*metabolism
MH  - Sumatriptan/metabolism
MH  - Triazoles/metabolism
MH  - Tritium
MH  - Tryptamines
EDAT- 1999/04/08 00:00
MHDA- 1999/04/08 00:01
CRDT- 1999/04/08 00:00
PHST- 1999/04/08 00:00 [pubmed]
PHST- 1999/04/08 00:01 [medline]
PHST- 1999/04/08 00:00 [entrez]
AID - S0014-2999(99)00026-6 [pii]
AID - 10.1016/s0014-2999(99)00026-6 [doi]
PST - ppublish
SO  - Eur J Pharmacol. 1999 Mar 5;368(2-3):259-68. doi: 10.1016/s0014-2999(99)00026-6.