PubMed · 14137170
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J MELON. 1964-02-01. [NOSE DROPS].. https://pubmed.ncbi.nlm.nih.gov/14137170/
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Clinically used anesthetics show amnestic, sedative, hypnotic and immobilizing properties. On a molecular level these drugs affect several receptors in the cell membrane of neurons. By using genetically engineered mice a linkage can now be made between actions on certain receptors and clinically desired and undesired effects. Experiments show that a certain GABA(A) receptor subtype mediates hypnosis and immobility, whereas another subtype is involved in side-effects like sedation and hypothermia. These findings form the basis for the development of new drugs, acting highly specific and with fewer side-effects.
In a previous study, we reported that inactivation of the medial septum or the hippocampus by muscimol, a GABA(A) receptor agonist, potentiated the effects of a general anesthetic. In this study, we further investigated whether other structures that are connected to the septohippocampal system are involved in mediating general anesthesia. In freely behaving rats, muscimol (0.25 microg) or saline was infused intracerebrally into one of four areas-the supramammillary area (SUM), nucleus accumbens (NAC), ventral pallidum (VP), and ventral tegmental area (VTA)-and righting, pain, and EEG responses were recorded following either halothane or sodium pentobarbital, representing inhalational and injectable general anesthetic, respectively. The effect of halothane (2%) or pentobarbital (20 mg/kg i.p.) in abolishing the righting, pain response, or low-voltage neocortical activity was enhanced, and the initial behavioral hyperactivity (delirium) was reduced, after muscimol as compared to after saline infusion in SUM, NAC, VP, and VTA. EEGs in the hippocampus and the sensorimotor cortex following halothane or pentobarbital showed increased delta, and decreased hippocampal theta and gamma waves after muscimol infusion as compared to saline infusion in SUM, NAC, VP, and VTA. By contrast, infusion of muscimol in the median raphe increased locomotion and did not significantly alter the behavioral or EEG effects of halothane or pentobarbital. It is suggested that structures that activate the limbic cortices (MS, SUM, and VTA but not the median raphe) or mediate the output of the hippocampus (NAC and VP) normally participate in maintaining consciousness and inactivation of these structures potentiates the response to a general anesthetic.
L-adrenaline is often included in local anaesthetic (LA) solutions for injection to improve the quality of the anaesthetic block. The concentration of the LA is between 2.5 and 20 mg/ml and the concentration of adrenaline is typically < or = 0.1% of the LA concentration. In order to follow the racemization into d-adrenaline, not only is chiral separation needed but also sufficient resolution from the LA and other components of the injection solution. Furthermore, very high sensitivity is needed in order to be able to determine the d-enantiomer at very low concentrations, i.e. down to about 0.1 microg/ml. The development of a chiral capillary electrophoresis method that is able to determine the racemization of adrenaline is described, together with a limited validation. Samples are injected without pretreatment and analysed with a capillary electrophoresis buffer containing 40 mM heptakis(2,6-di-O-methyl)-beta-cyclodextrin, 0.10 M phosphoric acid and 0.05 M triethanolamine. The amounts of d-adrenaline found in the LA products tested were typically < 3% of the l-adrenaline concentration and < 0.003% of the LA concentration.