R M McKernan

Summary

Affiliation: Merck Research Laboratories
Country: USA

Publications

  1. ncbi request reprint Sedative but not anxiolytic properties of benzodiazepines are mediated by the GABA(A) receptor alpha1 subtype
    R M McKernan
    Neuroscience Research Centre, Merck Sharp and Dohme Research Laboratories, Terlings Park, Eastwick Road, Harlow, Essex CM20 2QR, UK
    Nat Neurosci 3:587-92. 2000
  2. ncbi request reprint Photoaffinity labeling of the benzodiazepine binding site of alpha1beta3gamma2 gamma-aminobutyric acidA receptors with flunitrazepam identifies a subset of ligands that interact directly with His102 of the alpha subunit and predicts orientation of these w
    R M McKernan
    Department of Biochemistry, Merck Sharp and Dohme Research Laboratories, Harlow, Essex, UK CM2O 2QR
    Mol Pharmacol 54:33-43. 1998
  3. ncbi request reprint Autoradiographic localization of alpha5 subunit-containing GABAA receptors in rat brain
    C Sur
    Department of Biochemistry, Merck Sharp and Dohme Research Laboratories, Terlings Park, Eastwick Road, Harlow, Essex, CM20 2QR, UK
    Brain Res 822:265-70. 1999
  4. pmc theta, a novel gamma-aminobutyric acid type A receptor subunit
    T P Bonnert
    Neuroscience Research Centre, Merck Sharp and Dohme Research Laboratories, Eastwick Road, Harlow, Essex CM20 2QR, England, UK
    Proc Natl Acad Sci U S A 96:9891-6. 1999
  5. doi request reprint Preclinical and clinical pharmacology of TPA023B, a GABAA receptor α2/α3 subtype-selective partial agonist
    J R Atack
    Neuroscience Research Centre, Merck Sharp and Dohme Research Laboratories, Harlow, UK
    J Psychopharmacol 25:329-44. 2011
  6. pmc Characterization of [35S]t-butylbicyclophosphorothionate ([35S]TBPS) binding to GABAA receptors in postmortem human brain
    J R Atack
    Neuroscience Research Centre, Merck Sharp and Dohme Research Laboratories, Terlings Park, Eastwick Road, Harlow, Essex, UK
    Br J Pharmacol 150:1066-74. 2007
  7. ncbi request reprint Preferential coassembly of alpha4 and delta subunits of the gamma-aminobutyric acidA receptor in rat thalamus
    C Sur
    Department of Biochemistry and Molecular Biology, Neuroscience Research Centre, Merck Research Laboratories, Harlow, Essex, United Kingdom
    Mol Pharmacol 56:110-5. 1999
  8. ncbi request reprint alpha4beta3delta GABA(A) receptors characterized by fluorescence resonance energy transfer-derived measurements of membrane potential
    C E Adkins
    Neuroscience Research Centre, Terlings Park, Merck Sharp and Dohme, Eastwick Road, Harlow, Essex, United Kingdom
    J Biol Chem 276:38934-9. 2001
  9. ncbi request reprint Loss of the major GABA(A) receptor subtype in the brain is not lethal in mice
    C Sur
    Neuroscience Research Center, Merck Sharp and Dohme Research Laboratories, Harlow, Essex, CM20 2QR, United Kingdom
    J Neurosci 21:3409-18. 2001
  10. doi request reprint MRK-409 (MK-0343), a GABAA receptor subtype-selective partial agonist, is a non-sedating anxiolytic in preclinical species but causes sedation in humans
    J R Atack
    Neuroscience Research Centre, Merck Sharp and Dohme Research Laboratories, Harlow, UK
    J Psychopharmacol 25:314-28. 2011

Collaborators

Detail Information

Publications16

  1. ncbi request reprint Sedative but not anxiolytic properties of benzodiazepines are mediated by the GABA(A) receptor alpha1 subtype
    R M McKernan
    Neuroscience Research Centre, Merck Sharp and Dohme Research Laboratories, Terlings Park, Eastwick Road, Harlow, Essex CM20 2QR, UK
    Nat Neurosci 3:587-92. 2000
    ..This finding suggests ways to improve anxiolytics and to develop drugs for other neurological disorders based on their specificity for GABA(A) receptor subtypes in distinct neuronal circuits...
  2. ncbi request reprint Photoaffinity labeling of the benzodiazepine binding site of alpha1beta3gamma2 gamma-aminobutyric acidA receptors with flunitrazepam identifies a subset of ligands that interact directly with His102 of the alpha subunit and predicts orientation of these w
    R M McKernan
    Department of Biochemistry, Merck Sharp and Dohme Research Laboratories, Harlow, Essex, UK CM2O 2QR
    Mol Pharmacol 54:33-43. 1998
    ..The data in the current study indicate that His102 interacts directly with the pendant phenyl group of diazepam, and further implications for the pharmacophore of the BZ binding site are discussed...
  3. ncbi request reprint Autoradiographic localization of alpha5 subunit-containing GABAA receptors in rat brain
    C Sur
    Department of Biochemistry, Merck Sharp and Dohme Research Laboratories, Terlings Park, Eastwick Road, Harlow, Essex, CM20 2QR, UK
    Brain Res 822:265-70. 1999
    ..These observations indicate that although [3H]L-655,708 binding sites have an overall low expression in rat CNS, they may contribute significantly to GABAergic inhibition in specific brain regions...
  4. pmc theta, a novel gamma-aminobutyric acid type A receptor subunit
    T P Bonnert
    Neuroscience Research Centre, Merck Sharp and Dohme Research Laboratories, Eastwick Road, Harlow, Essex CM20 2QR, England, UK
    Proc Natl Acad Sci U S A 96:9891-6. 1999
    ..This subunit has a unique distribution, with studies so far suggesting significant expression within monoaminergic neurons of both human and monkey brain...
  5. doi request reprint Preclinical and clinical pharmacology of TPA023B, a GABAA receptor α2/α3 subtype-selective partial agonist
    J R Atack
    Neuroscience Research Centre, Merck Sharp and Dohme Research Laboratories, Harlow, UK
    J Psychopharmacol 25:329-44. 2011
    ....
  6. pmc Characterization of [35S]t-butylbicyclophosphorothionate ([35S]TBPS) binding to GABAA receptors in postmortem human brain
    J R Atack
    Neuroscience Research Centre, Merck Sharp and Dohme Research Laboratories, Terlings Park, Eastwick Road, Harlow, Essex, UK
    Br J Pharmacol 150:1066-74. 2007
    ....
  7. ncbi request reprint Preferential coassembly of alpha4 and delta subunits of the gamma-aminobutyric acidA receptor in rat thalamus
    C Sur
    Department of Biochemistry and Molecular Biology, Neuroscience Research Centre, Merck Research Laboratories, Harlow, Essex, United Kingdom
    Mol Pharmacol 56:110-5. 1999
    ..In conclusion, our results show that in rat thalamus both alpha4betagamma2 and alpha4betadelta subtypes are expressed but alpha4betadelta is the major alpha4-containing GABAA receptor population...
  8. ncbi request reprint alpha4beta3delta GABA(A) receptors characterized by fluorescence resonance energy transfer-derived measurements of membrane potential
    C E Adkins
    Neuroscience Research Centre, Terlings Park, Merck Sharp and Dohme, Eastwick Road, Harlow, Essex, United Kingdom
    J Biol Chem 276:38934-9. 2001
    ..Pregnanolone was a particularly efficacious modulator of alpha(4)beta(3)delta receptors, consistent with a central role for this subunit combination in premenstrual syndrome...
  9. ncbi request reprint Loss of the major GABA(A) receptor subtype in the brain is not lethal in mice
    C Sur
    Neuroscience Research Center, Merck Sharp and Dohme Research Laboratories, Harlow, Essex, CM20 2QR, United Kingdom
    J Neurosci 21:3409-18. 2001
    ..Our data confirm that alpha1beta2gamma2 is the major GABA(A) receptor subtype in the murine brain and demonstrate that, surprisingly, the loss of this receptor subtype is not lethal...
  10. doi request reprint MRK-409 (MK-0343), a GABAA receptor subtype-selective partial agonist, is a non-sedating anxiolytic in preclinical species but causes sedation in humans
    J R Atack
    Neuroscience Research Centre, Merck Sharp and Dohme Research Laboratories, Harlow, UK
    J Psychopharmacol 25:314-28. 2011
    ..Thus, the preclinical non-sedating anxiolytic profile of MRK-409 did not translate into humans and further development of this compound was halted...
  11. ncbi request reprint Anticonvulsant and adverse effects of avermectin analogs in mice are mediated through the gamma-aminobutyric acid(A) receptor
    G R Dawson
    Merck Sharp and Dohme Research Laboratories, Neuroscience Research Centre, Terlings Park, Eastwick Road, Harlow, Essex, United Kingdom
    J Pharmacol Exp Ther 295:1051-60. 2000
    ..Because both anticonvulsant activity and toxicity correlated best with activity at GABA(A) receptors, it is unlikely that these effects can be separated, which may contraindicate the potential use of avermectins as anticonvulsants...
  12. ncbi request reprint Effect of alpha subunit on allosteric modulation of ion channel function in stably expressed human recombinant gamma-aminobutyric acid(A) receptors determined using (36)Cl ion flux
    A J Smith
    Merck Sharp and Dohme Research Laboratories, Neuroscience Research Centre, Harlow, Essex, United Kingdom
    Mol Pharmacol 59:1108-18. 2001
    ..The rank order of potentiation for pregnanolone was alpha5 > alpha2 > alpha3 = alpha4 > alpha1, for loreclezole alpha1 = alpha2 = alpha3 > alpha5 > alpha4, and for pentobarbital alpha4 = alpha5 = alpha2 > alpha1 = alpha3...
  13. ncbi request reprint N-(indol-3-ylglyoxylyl)piperidines: high affinity agonists of human GABA-A receptors containing the alpha1 subunit
    I Collins
    Department of Medicinal Chemistry, Merck Sharp and Dohme Research Laboratories, Neuroscience Research Centre, Harlow, Essex, UK
    Bioorg Med Chem Lett 10:1381-4. 2000
    ..All three receptor subtypes discriminate substantially between the two enantiomers of the chiral ligand 10...
  14. ncbi request reprint Molecular and functional diversity of the expanding GABA-A receptor gene family
    P J Whiting
    Neuroscience Research Centre, Merck Sharp and Dohme Research Laboratories, Harlow, Essex, England, UK
    Ann N Y Acad Sci 868:645-53. 1999
    ..The structure, function, and distribution of theta-containing receptors, and receptors containing the recently reported epsilon subunit, are described...
  15. ncbi request reprint Ligand-gated ion channel subunit partnerships: GABAA receptor alpha6 subunit gene inactivation inhibits delta subunit expression
    A Jones
    Medical Research Council Laboratory of Molecular Biology, Medical Research Council Centre, Cambridge CB2 2QH, United Kingdom
    J Neurosci 17:1350-62. 1997
    ..Because in alpha6 -/- neurons the remaining alpha1, beta2/3, and gamma2 subunits cannot rescue the delta subunit, certain potential subunit combinations may not be found in wild-type cells...
  16. pmc Another mechanism for creating diversity in gamma-aminobutyrate type A receptors: RNA splicing directs expression of two forms of gamma 2 phosphorylation site
    P Whiting
    Neuroscience Research Centre, Merck Sharp and Dohme Research Laboratories, Harlow, Essex, U K
    Proc Natl Acad Sci U S A 87:9966-70. 1990
    ..This mechanism for creating GABAA receptor diversity may allow differential regulation of the function of receptor subtypes...