Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 2 de 2
Filter
Add more filters










Database
Language
Publication year range
1.
Eur J Clin Pharmacol ; 71(7): 773-99, 2015 Jul.
Article in English | MEDLINE | ID: mdl-26008212

ABSTRACT

BACKGROUND: The following review is a compilation of the recent advances and knowledge on the behaviour of the most frequently used compounds to treat inflammatory bowel disease in an organism. RESULTS: It considers clinical aspects of each entity and the pharmacokinetic/pharmacodynamic relationship supported by the use of plasma monitoring, tissue concentrations, and certain aspects derived from pharmacogenetics.


Subject(s)
Anti-Inflammatory Agents/pharmacokinetics , Anti-Inflammatory Agents/therapeutic use , Colitis, Ulcerative/drug therapy , Crohn Disease/drug therapy , Gastrointestinal Agents/pharmacokinetics , Gastrointestinal Agents/therapeutic use , Animals , Anti-Inflammatory Agents/adverse effects , Colitis, Ulcerative/diagnosis , Colitis, Ulcerative/immunology , Crohn Disease/diagnosis , Crohn Disease/immunology , Drug Monitoring , Gastrointestinal Agents/adverse effects , Humans , Pharmacogenetics , Remission Induction , Treatment Outcome
2.
Neuroscience ; 297: 47-57, 2015 Jun 25.
Article in English | MEDLINE | ID: mdl-25839150

ABSTRACT

Prialt, a synthetic version of Ca(v)2.2 antagonist ω-conotoxin MVIIA derived from Conus magus, is the first clinically approved voltage-gated calcium channel blocker for refractory chronic pain. However, due to the narrow therapeutic window and considerable side effects associated with systemic dosing, Prialt is only administered intrathecally. N-triazole oxindole (TROX-1) is a novel use-dependent and activation state-selective small-molecule inhibitor of Ca(v)2.1, 2.2 and 2.3 calcium channels designed to overcome the limitations of Prialt. We have examined the neurophysiological and behavioral effects of blocking calcium channels with TROX-1. In vitro, TROX-1, in contrast to state-independent antagonist Prialt, preferentially inhibits Ca(v)2.2 currents in rat dorsal root ganglia (DRG) neurons under depolarized conditions. In vivo electrophysiology was performed to record from deep dorsal horn lamina V/VI wide dynamic range neurons in non-sentient spinal nerve-ligated (SNL) and sham-operated rats. In SNL rats, spinal neurons exhibited reduced responses to innocuous and noxious punctate mechanical stimulation of the receptive field following subcutaneous administration of TROX-1, an effect that was absent in sham-operated animals. No effect was observed on neuronal responses evoked by dynamic brushing, heat or cold stimulation in SNL or sham rats. The wind-up response of spinal neurons following repeated electrical stimulation of the receptive field was also unaffected. Spinally applied TROX-1 dose dependently inhibited mechanically evoked neuronal responses in SNL but not sham-operated rats, consistent with behavioral observations. This study confirms the pathological state-dependent actions of TROX-1 through a likely spinal mechanism and reveals a modality selective change in calcium channel function following nerve injury.


Subject(s)
Calcium Channel Blockers/pharmacology , Ganglia, Spinal/pathology , Indoles/pharmacology , Peripheral Nerve Injuries/pathology , Sensory Receptor Cells/drug effects , Spinal Nerves/pathology , Triazoles/pharmacology , Acetone/pharmacology , Action Potentials/drug effects , Animals , Calcium Channel Blockers/chemistry , Disease Models, Animal , Dose-Response Relationship, Drug , Electric Stimulation , Hyperalgesia/physiopathology , Indoles/chemistry , Male , Pain Measurement , Pain Threshold/drug effects , Patch-Clamp Techniques , Rats , Rats, Sprague-Dawley , Triazoles/chemistry , omega-Conotoxins/pharmacology
SELECTION OF CITATIONS
SEARCH DETAIL
...