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Positive allosteric modulators as an approach to nicotinic acetylcholine receptor-targeted therapeutics: advantages and limitations.
This review discusses models for the activation and desensitization of nAChR, and the discovery of multiple types of ligands that influence those processes in both heteromeric nA ChR, such as the high-affinity nicotine receptors of the brain, and homomeric α7-type receptors.
Analysis of mecamylamine stereoisomers on human nicotinic receptor subtypes.
It is suggested that in chronic (i.e., therapeutic) application, S-(+)-mecamylamine might be preferable to R-(-)-micylamine in terms of equilibrium inactivation of neuronal receptors with decreased side effects associated with muscle-type receptors.
TC-5619: an alpha7 neuronal nicotinic receptor-selective agonist that demonstrates efficacy in animal models of the positive and negative symptoms and cognitive dysfunction of schizophrenia.
The results suggest that alpha7-selective agonists such as TC-5619, either alone or in combination with antipsychotics, could offer a new approach to treating the constellation of symptoms associated with schizophrenia, including cognitive dysfunction.
Investigation of the Molecular Mechanism of the α7 Nicotinic Acetylcholine Receptor Positive Allosteric Modulator PNU-120596 Provides Evidence for Two Distinct Desensitized States
The characterization of prolonged bursts of single-channel currents that occur with PNU-120596 provide a remarkable contrast to the behavior of the channels in the absence of the PAM, which shows a 100,000-fold increase in Popen compared with receptors in the nonpotentiated state.
An evaluation of neuronal nicotinic acetylcholine receptor activation by quaternary nitrogen compounds indicates that choline is selective for the α7 subtype
Physiological concentrations of choline desensitize alpha 7 receptors to ACh suggesting that, in vivo, choline may regulate both the activation and inactivation of this receptor.
Analysis of 3-(4-hydroxy, 2-Methoxybenzylidene)anabaseine selectivity and activity at human and rat alpha-7 nicotinic receptors.
The studies suggest that the efficacy of GTS-21 in primates may depend on a pro-drug function, and 4OH-G TS-21 was protective in both human and rat cell lines, although GTS -21 was effective only in the latter.
Merging old and new perspectives on nicotinic acetylcholine receptors.
  • R. Papke
  • Biology, Medicine
    Biochemical pharmacology
  • 1 May 2014
This review presents perspectives on the pharmacology and therapeutic targeting of nAChRs for the treatment of nicotine dependence or disease.
Intrinsically Low Open Probability of α7 Nicotinic Acetylcholine Receptors Can Be Overcome by Positive Allosteric Modulation and Serum Factors Leading to the Generation of Excitotoxic Currents at
Despite reduced potentiation at body temperatures, use of type II positive allosteric modulators may put cells that naturally express high levels of α7 nAChRs, such as neurons in the hippocampus and hypothalamus, at risk.
Activation and Inhibition of Mouse Muscle and Neuronal Nicotinic Acetylcholine Receptors Expressed in Xenopus Oocytes
The data indicate that, as with receptors cloned from other species, pairwise expression of neuronal α and β subunits in oocytes generates heterogeneous populations of receptors, most likely caused by variations in subunit stoichiometry.
Partial agonist properties of cytisine on neuronal nicotinic receptors containing the beta 2 subunit.
It is suggested that cytisine is a true partial agonist for beta 2-containing ACh receptors and as such can inhibit the response of these receptors to ACh through a competitive mechanism.