The effects of fentanyl-like opioids and hydromorphone on human 5-HT3A receptors.

Background: 5-HT(3) receptors are involved in various physiologic functions, including the modulation of emesis. 5-HT(3) antagonists are clinically widely used as potent antiemetics. Emesis is also a side effect of opioid analgesics.

Molecular actions of propofol on human 5-HT3A receptors: enhancement as well as inhibition by closely related phenol derivatives.

Background: 5-Hydroxytryptamine type 3 (5-HT3) receptors are excitatory ligand-gated ion channels which are involved in postoperative nausea and vomiting. They are depressed by the anesthetic propofol, which, in contrast, enhances the activity of inhibitory ligand-gated ion channels such as gamma-aminobutyric acid type A receptors and glycine receptors. To investigate the molecular mechanisms responsible for these contrasting actions, we examined the kinetics of the action of propofol and its lesser hydrophobic derivatives 2-isopropylphenol and phenol on human 5-HT3A receptors.

Interactions of anesthetics with their targets: non-specific, specific or both?

What makes a general anesthetic a general anesthetic? We shall review first what general anesthesia is all about and which drugs are being used as anesthetics. There is neither a unique definition of general anesthesia nor any consensus on how to measure it. Diverse drugs and combinations of drugs generate general anesthetic states of sometimes very different clinical quality.

Effects of tramadol and O-demethyl-tramadol on human 5-HT reuptake carriers and human 5-HT3A receptors: a possible mechanism for tramadol-induced early emesis.

([3H]5-HT)-uptake and patch-clamp techniques were used to study the actions of (+) and (-) tramadol and the active metabolites of tramadol, (+) and (-) O-demethyl-tramadol on the human serotonin (5-HT) transporter and the human 5-HT3A receptor, stably expressed in HEK-293 cells. The (+) and (-) enantiomers of tramadol suppressed the human 5-HT transporter concentration-dependently (IC50=1.0 and 0.

Differential lidocaine sensitivity of human voltage-gated potassium channels relevant to the auditory system.

Hypothesis: Lidocaine may lead to an alteration in the processing of hearing as observed during tinnitus by inhibiting voltage-gated potassium channels at clinically relevant concentrations.

Background: Recent molecular evidence suggests that the voltage-gated potassium channels Kv 3.1 and Kv 1.

Interactions of metoclopramide and ergotamine with human 5-HT(3A) receptors and human 5-HT reuptake carriers.

The actions of metoclopramide and ergotamine, drugs which are used as a combined migraine medication, on human (h)5-HT3A receptors and 5-HT reuptake carriers, stably expressed in HEK-293 cells, were studied with patch-clamp- and ([3H]5-HT)-uptake techniques. At clinical concentrations, metoclopramide inhibited peak and integrated currents through h5-HT3A receptors concentration-dependently (IC50 = 0.064 and 0.

Single sodium channels from human skeletal muscle in planar lipid bilayers: characterization and response to pentobarbital.

Purpose: To investigate the response to general anesthetics of different sodium-channel subtypes, we examined the effects of pentobarbital, a close thiopental analogue, on single sodium channels from human skeletal muscle and compared them to existing data from human brain and human ventricular muscle channels.

Methods: Sodium channels from a preparation of human skeletal muscle were incorporated into planar lipid bilayers, and the steady-state behavior of single sodium channels and their response to pentobarbital was examined in the presence of batrachotoxin, a sodium-channel activator. Single-channel currents were recorded before and after the addition of pentobarbital (0.

Monitoring of immobility to noxious stimulation during sevoflurane anesthesia using the spinal H-reflex.

Background: The spinal H-reflex has been shown to correlate with surgical immobility, i.e., the absence of motor responses to noxious stimulation, during isoflurane anesthesia.

Anticonvulsant pharmacology of voltage-gated Na+ channels in hippocampal neurons of control and chronically epileptic rats.

Voltage-gated Na+ channels are a main target of many first-line anticonvulsant drugs and their mechanism of action has been extensively investigated in cell lines and native neurons. Nevertheless, it is unknown whether the efficacy of these drugs might be altered following chronic epileptogenesis. We have, therefore, analysed the effects of phenytoin (100 micro m), lamotrigine (100 micro m) and valproate (600 micro m) on Na+ currents in dissociated rat hippocampal granule neurons in the pilocarpine model of chronic epilepsy.

A novel mechanism underlying drug resistance in chronic epilepsy.

The development of resistance to pharmacological treatment is common to many human diseases. In chronic epilepsy, many patients develop resistance to anticonvulsant drug treatment during the course of their disease, with the underlying mechanisms remaining unclear. We have studied cellular mechanisms underlying drug resistance in resected hippocampal tissue from patients with temporal lobe epilepsy by comparing two groups of patients, the first displaying a clinical response to the anticonvulsant carbamazepine and a second group with therapy-resistant seizures.

Propofol and sevoflurane in subanesthetic concentrations act preferentially on the spinal cord: evidence from multimodal electrophysiological assessment.

Background: Animal experiments in recent years have shown that attenuation of motor responses by general anesthetics is mediated at least partly by spinal mechanisms. Less is known about the relative potency of anesthetic drugs in suppressing cortical and spinal electrophysiological responses in vivo in humans, particularly those, but not only those, connected with motor responses. Therefore, we studied the effects of sevoflurane and propofol in humans using multimodal electrophysiological assessment.