Gabapentin is not a GABA B receptor agonist

Gabapentin is not a GABA B receptor agonist Recent experiments have demonstrated that formation of functional type B gamma-aminobutyric acid (GABA B ) receptors requires co-expression of two receptor subunits, GABA B1 and GABA B2 . Despite the identification of these subunits and a number of associated splice variants, there has been little convincing evidence of pharmacological diversity between GABA B receptors comprising different subunit combinations. However, Ng et al. (Mol. Pharmacol., 59 (2000) 144) have recently suggested a novel and important pharmacological difference between GABA B receptor heterodimers expressing the GABA B1a and GABA B1b receptor subunits. This study suggested that the antiepileptic GABA analogue gabapentin (Neurontin) is an agonist at GABA B receptors expressing the GABA B1a but not the GABA B1b receptor subunit. The importance of this finding with respect to identifying novel GABA B receptor subunit specific agonists prompted us to repeat these experiments in our own ( 35 S )− GTPγS binding and second messenger assay systems. Here we report that gabapentin was completely inactive at recombinant GABA B heterodimers expressing either GABA B1a or GABA B1b receptor subunits in combination with GABA B2 receptor subunits. In addition, in both CA1 and CA3 pyramidal neurones from rodent hippocampal slices we were unable to demonstrate any agonist-like effects of gabapentin at either pre- or post-synaptic GABA B receptors. In contrast, gabapentin activated a GABA A receptor mediated chloride conductance. Our data suggest that gabapentin is not a GABA B -receptor agonist let alone a GABA B receptor subunit selective agonist. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Neuropharmacology Elsevier

Loading next page...
 
/lp/elsevier/gabapentin-is-not-a-gaba-b-receptor-agonist-9P5d2HsuuM
Publisher
Elsevier
Copyright
Copyright © 2001 Elsevier Ltd
ISSN
0028-3908
eISSN
1873-7064
DOI
10.1016/S0028-3908(01)00140-X
Publisher site
See Article on Publisher Site

Abstract

Recent experiments have demonstrated that formation of functional type B gamma-aminobutyric acid (GABA B ) receptors requires co-expression of two receptor subunits, GABA B1 and GABA B2 . Despite the identification of these subunits and a number of associated splice variants, there has been little convincing evidence of pharmacological diversity between GABA B receptors comprising different subunit combinations. However, Ng et al. (Mol. Pharmacol., 59 (2000) 144) have recently suggested a novel and important pharmacological difference between GABA B receptor heterodimers expressing the GABA B1a and GABA B1b receptor subunits. This study suggested that the antiepileptic GABA analogue gabapentin (Neurontin) is an agonist at GABA B receptors expressing the GABA B1a but not the GABA B1b receptor subunit. The importance of this finding with respect to identifying novel GABA B receptor subunit specific agonists prompted us to repeat these experiments in our own ( 35 S )− GTPγS binding and second messenger assay systems. Here we report that gabapentin was completely inactive at recombinant GABA B heterodimers expressing either GABA B1a or GABA B1b receptor subunits in combination with GABA B2 receptor subunits. In addition, in both CA1 and CA3 pyramidal neurones from rodent hippocampal slices we were unable to demonstrate any agonist-like effects of gabapentin at either pre- or post-synaptic GABA B receptors. In contrast, gabapentin activated a GABA A receptor mediated chloride conductance. Our data suggest that gabapentin is not a GABA B -receptor agonist let alone a GABA B receptor subunit selective agonist.

Journal

NeuropharmacologyElsevier

Published: Dec 1, 2001

References

  • GABA B receptor pharmacology
    Bowery, N.G
  • Cloning and tissue distribution of novel splice variants of the rat GABA B receptor
    Isomoto, S; Kaibara, M; Sakurai-Yamashita, Y; Nagayama, Y; Uezono, Y; Yano, K; Taniyama, K
  • A summary of mechanistic hypotheses of gabapentin pharmacology
    Taylor, C.P; Gee, N.S; Su, T.-Z; Kocsis, J.D; Welty, D.F; Brown, J.P; Dooley, D.J; Boden, P; Singh, L
  • Calcium sensing properties of the GABA B receptor
    Wise, A; Green, A; Main, M.J; Wilson, R; Fraser, N; Marshall, F.H

You’re reading a free preview. Subscribe to read the entire article.


DeepDyve is your
personal research library

It’s your single place to instantly
discover and read the research
that matters to you.

Enjoy affordable access to
over 18 million articles from more than
15,000 peer-reviewed journals.

All for just $49/month

Explore the DeepDyve Library

Search

Query the DeepDyve database, plus search all of PubMed and Google Scholar seamlessly

Organize

Save any article or search result from DeepDyve, PubMed, and Google Scholar... all in one place.

Access

Get unlimited, online access to over 18 million full-text articles from more than 15,000 scientific journals.

Your journals are on DeepDyve

Read from thousands of the leading scholarly journals from SpringerNature, Elsevier, Wiley-Blackwell, Oxford University Press and more.

All the latest content is available, no embargo periods.

See the journals in your area

DeepDyve

Freelancer

DeepDyve

Pro

Price

FREE

$49/month
$360/year

Save searches from
Google Scholar,
PubMed

Create folders to
organize your research

Export folders, citations

Read DeepDyve articles

Abstract access only

Unlimited access to over
18 million full-text articles

Print

20 pages / month

PDF Discount

20% off