RESUMEN
The ultra-short-acting opioid analgesic remifentanil provided the approach that was used in the synthesis of remimazolam. A carboxylic ester was incorporated into the benzodiazepine structure providing a resultant compound that is rapidly broken down in the body into a breakdown product that is inactive, thus ensuring a very short-acting benzodiazepine. Remimazolam is highly selective in its action, only having activity at the GABAA receptor. It has been shown to be highly effective in providing sedation for bronchoscopy and colonoscopy without having a prolonged duration of action, therefore having a short effect until patients are fully awake and ready for discharge.
Asunto(s)
Benzodiazepinas , Hipnóticos y Sedantes , Benzodiazepinas/efectos adversos , Humanos , Hipnóticos y Sedantes/efectos adversosRESUMEN
INTRODUCTION: Neuropathic pain can be very difficult to treat and it is one of the important medical challenging about pain treatments. Muscimol as a new agonist of gamma-Aminobutyric acid receptor type A (GABAA) have been introduced for pain management. Thus, the present study was performed to evaluate the pain alleviating effect of intrathecal injection of different doses of muscimol as GABAA receptor agonist in spinal cord injury (SCI) model of neuropathic pain. METHODS: In the present experimental study, male Wistar rats were treated by muscimol 0.01, 0.1 or 1 µg/10ul, intrathecally (i.t.) three weeks after induction of spinal cord injury using compression injury model. Neuropathic pain symptoms were assessed at before treatment, 15 minutes, one hour and three hours after muscimol administration. The time of peak effect and optimum dosage was assessed by repeated measures analysis of variance and analysis of covariance, respectively. RESULTS: Muscimol with the dose of 0.01 µg in 15 minutes caused to improve the thermal hyperalgesia (df: 24, 5; F= 6.6; p<0.001), mechanical hyperalgesia (df: 24, 5; F= 7.8; p<0.001), cold allodynia (df: 24, 5; F= 6.96; p<0.001), and mechanical allodynia (df: 24, 5; F= 15.7; p<0.001). The effect of doses of 0.1 µg and 1 µg were also significant. In addition, the efficacy of different doses of muscimol did not have difference on thermal hyperalgesia (df: 24, 5; F= 1.52; p= 0.24), mechanical hyperalgesia (df: 24, 5; F= 0.3; p= -0.75), cold allodynia (df: 24, 5; F= 0.8; p= -0.56), and mechanical allodynia (df: 24, 5; F= 1.75; p= 0.86). CONCLUSION: The finding of the present study revealed that using muscimol with doses of 0.01µg, 0.1µg, and 1 µg reduces the symptoms of neuropathic pain. In addition, the effect of GABAA agonist is short term and its effectiveness gradually decreases by time.
RESUMEN
We have made use of the δ subunit-selective allosteric modulator DS2 (4-chloro-N-[2-(2-thienyl)imidazo[1,2-a]pyridine-3-yl benzamide) to assay the contribution of δ-GABAARs to tonic and phasic conductance changes in the cerebellum, thalamus and neocortex. In cerebellar granule cells, an enhancement of the tonic conductance was observed for DS2 and the orthosteric agonist THIP (4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol). As expected, DS2 did not alter the properties of GABAA receptor-mediated inhibitory postsynaptic synaptic conductances (IPSCs) supporting a purely extrasynaptic role for δ-GABAARs in cerebellar granule cells. DS2 also enhanced the tonic conductance recorded from thalamic relay neurons of the visual thalamus with no alteration in IPSC properties. However, in addition to enhancing the tonic conductance DS2 also slowed the decay of IPSCs recorded from layer II/III neocortical neurons. A slowing of the IPSC decay also occurred in the presence of the voltage-gated sodium channel blocker TTX. Moreover, under conditions of reduced GABA release the ability of DS2 to enhance the tonic conductance was attenuated. These results indicate that δ-GABAARs can be activated following vesicular GABA release onto neocortical neurons and that the actions of DS2 on the tonic conductance may be influenced by the ambient GABA levels present in particular brain regions.