Riluzole, a glutamate release inhibitor, induces loss of righting reflex, antinociception, and immobility in response to noxious stimulation in mice.

BACKGROUND: The general anesthetic state comprises behavioral and perceptual components, including amnesia, unconsciousness, analgesia, and immobility. In vitro, glutamatergic excitatory neurons are important targets for anesthetic action at the cellular and microcircuits levels. Riluzole (2-amino-6-[trifluoromethoxy]benzothiazole) is a neuroprotective drug that inhibits glutamate release from nerve terminals in the central nervous system. Here, we examined in vivo the ability of riluzole to produce components of the general anesthetic state through a selective blockade of glutamatergic neurotransmission. METHODS: Riluzole was administered intraperitoneally in adult male ddY mice. To assess the general anesthetic components, three end-points were used: 1) loss of righting reflex (LORR; as a measure of unconsciousness), 2) loss of movement in response to noxious stimulation (as a measure of immobility), and 3) loss of nociceptive response (as a measure of analgesia). RESULTS: The intraperitoneal administration of riluzole induced LORR in a dose-dependent fashion with a 50% effective dose value of 27.4 (23.3-32.2; 95% confidence limits) mg/kg. The behavioral and microdialysis studies revealed that time-course changes in impairment and LORR induced by riluzole corresponded with decreased glutamate levels in the mouse brain. This suggests that riluzole-induced LORR (unconsciousness) could result, at least in part, from its ability to decrease brain glutamate concentrations. Riluzole dose-dependently produced not only LORR, but also loss of movement in response to painful stimulation (immobility), and loss of nociceptive response (analgesia) with 50% effective dose values of 43.0 (37.1-49.9), and 10.0 (7.4-13.5) mg/kg, respectively. These three dose-response curves were parallel, suggesting that the behavioral effects of riluzole may be mediated through a common site of action. CONCLUSIONS: These findings suggest that riluzole-induced LORR, immobility, and antinociception appear to be associated with its ability to inhibit glutamatergic neurotransmission in the central nervous system.

An alternative approach to the monitoring of respiration by dynamic air-pressure sensor.

Monitoring and assessing of patient respiratory function during conscious sedation are important because many drugs used for conscious sedation produce respiratory depression and subsequent hypoventilation. The purpose of this study is to assess the value of a dynamic air-pressure sensor for respiratory monitoring of clothed patients. Eight clothed adult volunteers were reclined on a dental chair positioned horizontally. The air bag for measuring air-pressure signals corresponding to respiration was placed on the seat back of the dental chair in the central lumbar area of the subject. The subject breathed through a face mask with a respirometer attached for measuring expiratory tidal volume. The air-pressure signals corresponding to respiration were obtained and the time integration values for air pressure during each expiration (integral P(exp)) were calculated. The expiratory tidal volume (TV(exp)) was measured simultaneously by respirometer. The relationship between TV(exp) and integral P(exp) for each subject was assessed by a Pearson correlation coefficient. A strong correlation between TV(exp) and integral P(exp) was observed in all subjects. Measuring integral P(exp) by dynamic air-pressure sensor makes it possible to estimate respiratory volume breath by breath, and the respiratory pressure-time integral waveform was useful in visually monitoring the respiration pattern. We believe that in the future this device will be used to monitor respiratory physiology in clothed patients, contributing to safer sedative procedures.