Enhancement of GABAergic Activity: Neuropharmacological Effects of Benzodiazepines and Therapeutic Use in Anesthesiology

Saari, Teijo I.; Uusi‐Oukari, Mikko; Ahonen, Jouni; Olkkola, Klaus T.

doi:10.1124/pr.110.002717

Cited by 116 publications

(90 citation statements)

References 278 publications

(344 reference statements)

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“…Among human ligand-gated ion channels, GABA A receptors have been the most heavily targeted for drug development, yielding positive allosteric modulators, such as benzodiazepines, that are widely used as antianxiety and sedative drugs (Saari et al, 2011). In addition, many surgical procedures involve drugs such as midazolam and propofol, which are employed to enhance GABA A function (Sneyd and Rigby-Jones, 2010).…”

Section: Opportunities For Novel Drug Design For Under-targeted LImentioning

confidence: 99%

Seeking Structural Specificity: Direct Modulation of Pentameric Ligand-Gated Ion Channels by Alcohols and General Anesthetics

Howard

Trudell

Harris³

2014

Pharmacol Rev

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Section: Opportunities For Novel Drug Design For Under-targeted LImentioning

confidence: 99%

Seeking Structural Specificity: Direct Modulation of Pentameric Ligand-Gated Ion Channels by Alcohols and General Anesthetics

Howard

Trudell

Harris³

2014

Pharmacol Rev

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“…Currently, allosteric modulation of GABA A ligand-gated ion channels is a well-exploited mechanism for general anesthetics, benzodiazepine pre-anesthetic medications, and anxiolytics [65][66][67]. Agonist potentiation is also being explored to mitigate the side effects of poorly tolerated but otherwise effective analgesics acting on, for example, GABA B receptors [68] and nicotinic acetylcholine receptors [69].…”

Section: Discussionmentioning

confidence: 99%

Positive allosteric modulation of TRPV1 as a novel analgesic mechanism

Lebovitz

Kaszás

Keller

et al. 2012

The Journal of Pain

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Background: The prevalence of long-term opiate use in treating chronic non-cancer pain is increasing, and prescription opioid abuse and dependence are a major public health concern. To explore alternatives to opioid-based analgesia, the present study investigates a novel allosteric pharmacological approach operating through the cation channel TRPV1. This channel is highly expressed in subpopulations of primary afferent unmyelinated C-and lightly-myelinated Aδ-fibers that detect low and high rates of noxious heating, respectively, and it is also activated by vanilloid agonists and low pH. Sufficient doses of exogenous vanilloid agonists, such as capsaicin or resiniferatoxin, can inactivate/deactivate primary afferent endings due to calcium overload, and we hypothesized that positive allosteric modulation of agonist-activated TRPV1 could produce a selective, temporary inactivation of nociceptive nerve terminals in vivo. We previously identified MRS1477, a 1,4-dihydropyridine that potentiates vanilloid and pH activation of TRPV1 in vitro, but displays no detectable intrinsic agonist activity of its own. To study the in vivo effects of MRS1477, we injected the hind paws of rats with a non-deactivating dose of capsaicin, MRS1477, or the combination. An infrared diode laser was used to stimulate TRPV1-expressing nerve terminals and the latency and intensity of paw withdrawal responses were recorded. qRT-PCR and immunohistochemistry were performed on dorsal root ganglia to examine changes in gene expression and the cellular specificity of such changes following treatment.

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“…The basic pharmacodynamics is by modulation of the gamma-amino-butyric acid (GABA) effect, which is the dominating inhibitory neurotransmitter in the CNS. The benzodiazepines bind to GABA receptors in the CNS thereby suppressing activity in the nerve cells (Saari et al 2011). Their high lipophilicity allows quick passage across the blood-brain barrier to produce rapid onset of action.…”

Section: Benzodiazepinesmentioning

confidence: 99%

Dental Treatment under Sedation

Raadal¹

2013

Cognitive Behaviour Therapy for Dental Phobia and Anxiety

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Enhancement of GABAergic Activity: Neuropharmacological Effects of Benzodiazepines and Therapeutic Use in Anesthesiology

Cited by 116 publications

References 278 publications

Seeking Structural Specificity: Direct Modulation of Pentameric Ligand-Gated Ion Channels by Alcohols and General Anesthetics

Seeking Structural Specificity: Direct Modulation of Pentameric Ligand-Gated Ion Channels by Alcohols and General Anesthetics

Positive allosteric modulation of TRPV1 as a novel analgesic mechanism

Dental Treatment under Sedation

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