Immobilized anesthetic

Phencyclidine (PCP), one of the arylcyclohexylamines. was developed and originally used as a general anesthetic for humans. Due to psychotic and hallucinogenic reactions, use of the drug for humans was discontinued. It is now used legally only in veterinary medicine as an animal immobilizing agent. 

We have evidence that the female herself controls the mechanism by which one set of sperm is favored over the other. If females are anesthetized so as to inactivate their muscles, including presumably the many pumping muscles of their reproductive organs, the normal routing of sperm is inhibited. The anesthesia does not immobilize the sperm, indicating that it is not the sperm themselves that are in control of their fate (26). The reproductive system of female Utetheisa is a complex labyrinth of ducts and chambers. While we do not know precisely how... 

The mechanism of action of inhalational anesthetics is unknown. The diversity of chemical structures (inert gas xenon hydrocarbons halogenated hydrocarbons) possessing anesthetic activity appears to rule out involvement of specific receptors. According to one hypothesis, uptake into the hydrophobic interior of the plasmalemma of neurons results in inhibition of electrical excitability and impulse propagation in the brain. This concept would explain the correlation between anesthetic potency and lipophilicity of anesthetic drugs (A). However, an interaction with lipophilic domains of membrane proteins is also conceivable. Anesthetic potency can be expressed in terms of the minimal alveolar concentration (MAC) at which 50% of patients remain immobile following a defined painful stimulus (skin incision). Whereas the poorly lipophilic N2O must be inhaled in high concentrations (>70% of inspired air has to be replaced), much smaller concentrations (<5%) are required in the case of the more lipophilic halothane. 

Fluid membrane hypothesis Anesthetics stabilize, or rather immobilize the cell membrane, hampering membrane fluidity, which produces changes in the ion channel action. 

It is true that a more hydrophobic anesthetic is more potent, but not all hydrophobic substances are anesthetics. There exist substances such as 1,2-dichlorohexafluorocyclobutane and 2, 3-dichlorooctafluorobutane that would be predicted to be anesthetic based on their hydrophobicity, but that do not have anesthetic properties. These substances are called either non-anesthetics or non-immobilizers depending on the behaviors that have been tested and found lacking (Koblin et ak, 1994). 

SNA was originally synthesized and developed as an anesthetic agent for human use by Parke, Davis and Co. under the name Sernyl.13-15 its human use was soon abandoned, because It sometimes produced postoperative thought disturbances and agitation. It is currently used, under the name Sernylan, as an immobilizing agent in veterinary medicine. 

Both compounds (1 and 2) almost equally caused decrease of arterial blood pressure in a dose dependent and reversible manner at the dose of between 0.1 and 3 mg/kg, i.v. in pentobarbital-anesthetized as well as in un-anesthetized, gallamine-immobilized rabbits, Fig. (5), [58]. 

Depth of anesthesia is determined by the concentration of anesthetic agent that reaches the brain. Brain concentration, in turn, depends on the solubility and transport of the anesthetic agent in the bloodstream and on its partial pressure in inhaled air. Anesthetic potency is usually expressed as a minimum alveolar concentration (MAC), defined as the percent concentration of anesthetic in inhaled air that results in anesthesia in 50% of patients. As shown in Table 9.6, nitrous oxide, N2O, is the least potent of the common anesthetics. Fewer than 50% of patients are immobilized by breathing an 80 20 mix of nitrous oxide and oxygen. Methoxyflurane is the most potent agent a partial pressure of only 1.2 mm Hg is sufficient to anesthetize 50% of patients, and a partial pressure of 1.4 mm Hg will anesthetize 95%. 

Fig. 12.3. Time course of sonographic enhancement by LCM of Novikoff hepatoma in anesthetized rats using an immobilized transducer. These representative rat liver scans were obtained before injection, and 2, 30, and 60 minutes after i.v. injection, respectively. Arrows indicate the relatively bright, contrast-enhanced tumor area in the liver (within the image plane) at 2 minutes after injection. Contrariwise, the same area before injection (first panel) is only slightly hyperechoic compared with the surrounding normal liver parenchyma. (Taken from ref. 528.)...

Alternative survival methods include anesthesia by inhalation (isoflurane) or injectable (tribromoethanol) anesthetics which can be used to temporarily immobilize the mice (60, 61). While isoflurane is commonly used for repeated anesthesias, tribromoethanol is contraindicated for repeated use (60). Another approach for partial immobilization of mice is to use a 50-50% O2/CO2 mixture in a sealed container (see Note 3). Another alternative is to place the mice in a restraint device in which there is a black concave area for... 

Anesthetic potency can be expressed in terms of the minimal alveolar concentration (MAC) at which 50% of patients remain immobile following a defined painful stimulus (skin incision). Whereas the poorly lipophilic nitrous oxide must be inhaled in high concentrations, much smaller concentrations are required in the case of the more lipophilic halothane. 

Irritants (peripheral sensory irritants), lacrimators, sternutators, emetics, sedatives, hypnotics, serotonin antagonists, hypotensives, thermoregulator disrup-tors, nauseants, vision disruptors, neuromuscular blockers, malodorous substances, centrally acting anesthetics, immobilizers, tranquillizers. 

F Barbato, MI La Rotonda, F Quaglia. Chromatographic indexes on immobilized artificial membranes for local anesthetics relationships with activity data on closed sodium channels. Pharm Res 14 1699—1705, 1997. 

In an attempt to improve the selectivity of local dopamine measurements in the complex extracellular matrix of brain fluid, an implantable enzyme-based dopamine microbiosensor has been constructed based on the immobilization of tyrosinase in a thin-film chitosan coating of carbon-fiber disc microelectrodes [357]. o-Dopaquinone, which is the product of the tyrosinase reaction with dopamine, was monitored via its reduction at the modified microelectrode surface. The application of these cathodic tyrosinase dopamine microbiosensors was reported for the continuous real-time in vivo visualization of electrically stimulated dopamine release in the brain of anesthetized laboratory rats. Remarkably, due to the cathodic potential the sensor response was not significantly disturbed by the presence of typical interferences such as ascorbic and uric acid, serotonin, norepinephrine, and epinephrine. 

Components of the anesthetic state include amnesia, immobility in response to noxious stimulation, attenuation of autonomic responses to noxious stimulation, analgesia, and unconsciousness. General anesthesia is useful only insofar as it facilitates the performance of surgery or other noxious procedures. The performance of surgery usually requires an immobilized patient who does not have an excessive autonomic response to suigery (blood pressure and heart rate) and who has amnesia for the procedure. Thus, the essential components of the anesthetic state are immobilization, amnesia, and attenuation of autonomic responses to noxious stimulation. If an anesthetic produces profound amnesia, it can be difficult in principle to determine if it also produces either analgesia or unconsciousness. 

Clinical concentrations of inhalational anesthetics enhance the capacity of glycine to activate glycine-gated chloride channels (glycine receptors), which play an important role in inhibitory neurotransmission in the spinal cord and brainstem. Propofol, neurosteroids, and barbiturates also potentiate glycine-activated currents etomidate and ketamine do not. Subanesthetic concentrations of the inhalational anesthetics inhibit some classes of neuronal nicotinic ACh receptors these actions do not appear to mediate anesthetic immobilization but could mediate other components of anesthesia such as analgesia or amnesia. 

Fig. 1. Two-photon laser-scanning microscopy system and operation for exposing the inguinal lymph node, (a) Two-photon laser-scanning microscopy system including a Leica SP5 inverted 5-channel confocal microscope. (b)The cube and box, cube chamber, maintains temperature at 37.0°C 0.5°C. (c) Anesthetized mouse is shaved and has small Incision on flank, (d) Immobilized iLN with cyanoacrylate glue on blade fitted to chamber slide. To protect tissue from drying add a few drops of PBS to exposed iLN. (e) Mouse in a warmed chamber slide. Blade can hold exposed ILN preventing respiratory movements, (f) Complete set up for imaging. Mouse is anesfhefized by fhe infraperifoneal injecfion of avertin with an infusion set.

Anesthetize up to 12 females with ether or carbon dioxide and transfer to a drop of MRS on a silicone rubber dissecting plate. Quickly immobilize the flies by crushing their heads with forceps (brutal yet effective). 

Anesthetize frog Large, female Xenopus laevis frogs are put in ice water for 30 min or more, until all movement ceases. An ice bucket is filled nearly to the rim with ice and the immobile frog is placed on top of the ice, abdomen up. Ice is packed over the frog, leaving only a small area of lower abdomen visible. 

Despite a great deal of research, it is still not clear how anesthetics actually work. It is a near-universal characteristic of life that species ranging from tadpoles to humans can be reversibly immobilized. The search for the mechanisms by which this occurs is important, because it may lead us not only to safer anesthetics, but also to deeper understanding of what we mean by consciousness itself... 

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