David Triggle - Academia.edu (original) (raw)
Papers by David Triggle
![Research paper thumbnail of The influence of guanyl-5′-yl imidodiphosphate and sodium chloride on the binding of the muscarinic agonist, [3H] cis methyldioxolane](https://attachments.academia-assets.com/82844982/thumbnails/1.jpg)
](European Journal of Pharmacology, 1980
Molecular Pharmacology, 1976
Page 1. MOLECULAR PHARMACOLOGY, 12, 1019-1026 Copyright © 1976 by Academic Press, Inc. All rights... more Page 1. MOLECULAR PHARMACOLOGY, 12, 1019-1026 Copyright © 1976 by Academic Press, Inc. All rights of reproduction in any form reserved. Mechanism of Action of Benzilylcholine Mustard at the Muscarinic Receptor ...
[
J. Med. …, 2000
We report the synthesis of the single enantiomers of permanently charged dihydropyridine derivati... more We report the synthesis of the single enantiomers of permanently charged dihydropyridine derivatives (DHPs with alkyl linker lengths of two and eight carbon atoms) and their activities on cardiac and neuronal L-type calcium channels. Permanently charged chiral 1,4-dihydropyridines ...
Drug Development Research, 1984
This comparison of the binding characteristics and pharmacology of 1,4-dihydropyridines indicates... more This comparison of the binding characteristics and pharmacology of 1,4-dihydropyridines indicates that the high-affinity binding sites studied in cardiac and smooth muscle cells represent a major site of action of these drugs, and that this site is the Ca2+ channel or a closely related protein. Electrophysiological studies suggest that the effects of both Ca2+ channel inhibitors and activators are voltage dependent. The apparent lack of agreement between the equilibrium dissociation constants for [3H]1 ,4-dihydropyridines and their potency in cardiac muscle may be due to conformational modifications that occur in the 1,4-dihydropyridine binding site as a result of voltage or other changes during membrane isolation. The selective effect of 1 ,4-dihydropyridines for vascular smooth muscle relative to cardiac muscle may be explained, in part, by differences in membrane potentials and Ca2+ channel regulatory mechanisms and, in part, by differences in receptor structure. 1,4-Dihydropyridine antagonists and activators appear to bind to a common site that is not the same as the binding site for nondihydropyridine Ca2+ channel antagonists.
Drug Development Research, 2005
Abstract At a recent symposium in Noordwijkerhout, The Netherlands, the future of education in me... more Abstract At a recent symposium in Noordwijkerhout, The Netherlands, the future of education in medicinal chemistry was discussed in terms of its role in the drug discovery process. The questions posed included: What is the necessary knowledge basis for the medicinal ...
Fortschritte Der Arzneimittelforschung Progress in Drug Research Progres Des Recherches Pharmaceutiques, Feb 1, 1993
The pharmacology of the L-type Ca2+ channel has been the subject of considerable basic and clinic... more The pharmacology of the L-type Ca2+ channel has been the subject of considerable basic and clinical investigation over the past two decades primarily because of the clinical activities of nifedipine, verapamil and diltiazem. However, it is quite clear that this Ca2+ channel is, in common with other pharmacologic receptors, a multiple drug receptor. There are probably as many as six or more discrete drug binding sites associated with this Ca2+ channel. Continued investigation of these sites may yield both new therapeutic agents, structural clues to ligands active at other classes of Ca2+ channel and structures active at other classes of ion channel.
Principles of Medical Biology
ABSTRACT
Green and Sustainable Pharmacy, 2010
Journal of the Chemical Society, Perkin Transactions 1, 1991
Starting with 6-oxabicyclo [3.2. 1] oct-3-en-7-one 6, a three step, general synthetic route to bo... more Starting with 6-oxabicyclo [3.2. 1] oct-3-en-7-one 6, a three step, general synthetic route to both racemic and optically active 6-substituted 6-azabicyclo [3.2. 1] octan-3-ones has been developed. Opening of the lactone ring of 6 with amines gave amides which were reduced ...
Cellular and molecular neurobiology, 2003
1. The 1,4-dihydropyridine nucleus serves as the scaffold for important cardiovascular drugs-calc... more 1. The 1,4-dihydropyridine nucleus serves as the scaffold for important cardiovascular drugs-calcium antagonists-including nifedipine, nitrendipine, amlodipine, and nisoldipine, which exert their antihypertensive and antianginal actions through actions at voltage-gated calcium channels of the CaV1 (L-type) class. 2. These drugs act at a specific receptor site for which defined structure-activity relationships exist, including stereoselectivity. 3. Despite the widespread occurrence of the CaV1 class of channel, the calcium antagonists exhibit significant selectivity of action in the cardiovascular system. This selectivity arises from a number of factors including subtype of channel, state-dependent interactions. pharmacokinetics, and mode of calcium mobilization. 4. The 1,4-dihydropyridine nucleus is also a privileged structure or scaffold that can, when appropriately decorated substituents, interact at diverse receptors and ion channels, including potassium and sodium channels and r...
Pharmaceutical research, 1992
Radioligand binding affinities of seven muscarinic receptor ligands which possess an oxadiazole r... more Radioligand binding affinities of seven muscarinic receptor ligands which possess an oxadiazole ring side chain have been determined in rat heart, rat brain, and m1- or m3-transfected CHO cell membrane preparations to determine the selectivity for subtypes of muscarinic receptor. The ratios of binding constants in brain membranes were measured as an indicator of potential agonist activity against [3H]QNB and [3H]Oxo-M. These muscarinic ligands did not discriminate the subtypes of muscarinic receptors. Six muscarinic ligands which have a 3-amino- or 3-methyl-1,2,4-oxadiazol-5-yl groups attached to the 8-methyl-8-azabicyclo[3.2.1]oct-2-ene or 8-methyl-8-azabicyclo[3.2.1]octane head group show binding constants between 2.04 x 10(-6) and 1.79 x 10(-5) M in rat heart, rat brain, and m1- or m3-transfected CHO cell membrane preparations. 1-Methyl-2-[3-amino-1,2,4-oxadiazol-5-yl]piperidine shows low binding constants of approximately 10(-4) M in rat heart and rat brain. (1R,5S)-2-[3-Amino-1...
Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature
Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature
Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature
Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature
Chemical Communications (London)
Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature
Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature
Synthetic devices for traceless remote control of gene expression may provide new treatment oppor... more Synthetic devices for traceless remote control of gene expression may provide new treatment opportunities in future gene-and cell-based therapies. Here we report the design of a synthetic mind-controlled gene switch that enables human brain activities and mental states to wirelessly programme the transgene expression in human cells. An electroencephalography (EEG)-based brain-computer interface (BCI) processing mental state-specific brain waves programs an inductively linked wireless-powered optogenetic implant containing designer cells engineered for near-infrared (NIR) light-adjustable expression of the human glycoprotein SEAP (secreted alkaline phosphatase). The synthetic optogenetic signalling pathway interfacing the BCI with target gene expression consists of an engineered NIR light-activated bacterial diguanylate cyclase (DGCL) producing the orthogonal second messenger cyclic diguanosine monophosphate (c-di-GMP), which triggers the stimulator of interferon genes (STING)-dependent induction of synthetic interferon-b promoters. Humans generating different mental states (biofeedback control, concentration, meditation) can differentially control SEAP production of the designer cells in culture and of subcutaneous wirelesspowered optogenetic implants in mice.
Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature
European Journal of Pharmacology, 1980
Molecular Pharmacology, 1976
Page 1. MOLECULAR PHARMACOLOGY, 12, 1019-1026 Copyright © 1976 by Academic Press, Inc. All rights... more Page 1. MOLECULAR PHARMACOLOGY, 12, 1019-1026 Copyright © 1976 by Academic Press, Inc. All rights of reproduction in any form reserved. Mechanism of Action of Benzilylcholine Mustard at the Muscarinic Receptor ...
[
J. Med. …, 2000
We report the synthesis of the single enantiomers of permanently charged dihydropyridine derivati... more We report the synthesis of the single enantiomers of permanently charged dihydropyridine derivatives (DHPs with alkyl linker lengths of two and eight carbon atoms) and their activities on cardiac and neuronal L-type calcium channels. Permanently charged chiral 1,4-dihydropyridines ...
Drug Development Research, 1984
This comparison of the binding characteristics and pharmacology of 1,4-dihydropyridines indicates... more This comparison of the binding characteristics and pharmacology of 1,4-dihydropyridines indicates that the high-affinity binding sites studied in cardiac and smooth muscle cells represent a major site of action of these drugs, and that this site is the Ca2+ channel or a closely related protein. Electrophysiological studies suggest that the effects of both Ca2+ channel inhibitors and activators are voltage dependent. The apparent lack of agreement between the equilibrium dissociation constants for [3H]1 ,4-dihydropyridines and their potency in cardiac muscle may be due to conformational modifications that occur in the 1,4-dihydropyridine binding site as a result of voltage or other changes during membrane isolation. The selective effect of 1 ,4-dihydropyridines for vascular smooth muscle relative to cardiac muscle may be explained, in part, by differences in membrane potentials and Ca2+ channel regulatory mechanisms and, in part, by differences in receptor structure. 1,4-Dihydropyridine antagonists and activators appear to bind to a common site that is not the same as the binding site for nondihydropyridine Ca2+ channel antagonists.
Drug Development Research, 2005
Abstract At a recent symposium in Noordwijkerhout, The Netherlands, the future of education in me... more Abstract At a recent symposium in Noordwijkerhout, The Netherlands, the future of education in medicinal chemistry was discussed in terms of its role in the drug discovery process. The questions posed included: What is the necessary knowledge basis for the medicinal ...
Fortschritte Der Arzneimittelforschung Progress in Drug Research Progres Des Recherches Pharmaceutiques, Feb 1, 1993
The pharmacology of the L-type Ca2+ channel has been the subject of considerable basic and clinic... more The pharmacology of the L-type Ca2+ channel has been the subject of considerable basic and clinical investigation over the past two decades primarily because of the clinical activities of nifedipine, verapamil and diltiazem. However, it is quite clear that this Ca2+ channel is, in common with other pharmacologic receptors, a multiple drug receptor. There are probably as many as six or more discrete drug binding sites associated with this Ca2+ channel. Continued investigation of these sites may yield both new therapeutic agents, structural clues to ligands active at other classes of Ca2+ channel and structures active at other classes of ion channel.
Principles of Medical Biology
ABSTRACT
Green and Sustainable Pharmacy, 2010
Journal of the Chemical Society, Perkin Transactions 1, 1991
Starting with 6-oxabicyclo [3.2. 1] oct-3-en-7-one 6, a three step, general synthetic route to bo... more Starting with 6-oxabicyclo [3.2. 1] oct-3-en-7-one 6, a three step, general synthetic route to both racemic and optically active 6-substituted 6-azabicyclo [3.2. 1] octan-3-ones has been developed. Opening of the lactone ring of 6 with amines gave amides which were reduced ...
Cellular and molecular neurobiology, 2003
1. The 1,4-dihydropyridine nucleus serves as the scaffold for important cardiovascular drugs-calc... more 1. The 1,4-dihydropyridine nucleus serves as the scaffold for important cardiovascular drugs-calcium antagonists-including nifedipine, nitrendipine, amlodipine, and nisoldipine, which exert their antihypertensive and antianginal actions through actions at voltage-gated calcium channels of the CaV1 (L-type) class. 2. These drugs act at a specific receptor site for which defined structure-activity relationships exist, including stereoselectivity. 3. Despite the widespread occurrence of the CaV1 class of channel, the calcium antagonists exhibit significant selectivity of action in the cardiovascular system. This selectivity arises from a number of factors including subtype of channel, state-dependent interactions. pharmacokinetics, and mode of calcium mobilization. 4. The 1,4-dihydropyridine nucleus is also a privileged structure or scaffold that can, when appropriately decorated substituents, interact at diverse receptors and ion channels, including potassium and sodium channels and r...
Pharmaceutical research, 1992
Radioligand binding affinities of seven muscarinic receptor ligands which possess an oxadiazole r... more Radioligand binding affinities of seven muscarinic receptor ligands which possess an oxadiazole ring side chain have been determined in rat heart, rat brain, and m1- or m3-transfected CHO cell membrane preparations to determine the selectivity for subtypes of muscarinic receptor. The ratios of binding constants in brain membranes were measured as an indicator of potential agonist activity against [3H]QNB and [3H]Oxo-M. These muscarinic ligands did not discriminate the subtypes of muscarinic receptors. Six muscarinic ligands which have a 3-amino- or 3-methyl-1,2,4-oxadiazol-5-yl groups attached to the 8-methyl-8-azabicyclo[3.2.1]oct-2-ene or 8-methyl-8-azabicyclo[3.2.1]octane head group show binding constants between 2.04 x 10(-6) and 1.79 x 10(-5) M in rat heart, rat brain, and m1- or m3-transfected CHO cell membrane preparations. 1-Methyl-2-[3-amino-1,2,4-oxadiazol-5-yl]piperidine shows low binding constants of approximately 10(-4) M in rat heart and rat brain. (1R,5S)-2-[3-Amino-1...
Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature
Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature
Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature
Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature
Chemical Communications (London)
Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature
Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature
Synthetic devices for traceless remote control of gene expression may provide new treatment oppor... more Synthetic devices for traceless remote control of gene expression may provide new treatment opportunities in future gene-and cell-based therapies. Here we report the design of a synthetic mind-controlled gene switch that enables human brain activities and mental states to wirelessly programme the transgene expression in human cells. An electroencephalography (EEG)-based brain-computer interface (BCI) processing mental state-specific brain waves programs an inductively linked wireless-powered optogenetic implant containing designer cells engineered for near-infrared (NIR) light-adjustable expression of the human glycoprotein SEAP (secreted alkaline phosphatase). The synthetic optogenetic signalling pathway interfacing the BCI with target gene expression consists of an engineered NIR light-activated bacterial diguanylate cyclase (DGCL) producing the orthogonal second messenger cyclic diguanosine monophosphate (c-di-GMP), which triggers the stimulator of interferon genes (STING)-dependent induction of synthetic interferon-b promoters. Humans generating different mental states (biofeedback control, concentration, meditation) can differentially control SEAP production of the designer cells in culture and of subcutaneous wirelesspowered optogenetic implants in mice.
Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature