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Background Sterilization clinics often occur in remote places where anesthesia machines and compressed oxygen are unavailable. This study describes the use of total injectable anesthesia in dogs and cats presented for sterilization in a remote location. Results A total of 100 animals were sterilized; 26 female cats (CF), 22 male cats (CM), 28 female dogs (DF), and 24 male dogs (DM). CF were anesthetized with dexmedetomidine (20 mcg/kg), ketamine (8 mg/kg) and hydromorphone (0.1 mg/kg) IM. CM were anesthetized with dexmedetomidine (15 mcg/kg), ketamine (5 mg/kg) and hydromorphone (0.1 mg/kg) IM. Insufficient anesthesia in cats was treated with alfaxalone (1 mg/kg) IM. All cats were administered meloxicam at 0.3 mg/kg SQ. DF were anesthetized with dexmedetomidine (15 mcg/kg), ketamine (7–10 mg/kg) and hydromorphone (0.1 mg/kg) IM. DM were anesthetized with dexmedetomidine (15 mcg/kg), ketamine (5 mg/kg) and hydromorphone (0.1 mg/kg) IM. All dogs had IV catheter and endotracheal tube placed. If SpO2 Conclusion Total injectable anesthesia can be accomplished for remote location sterilization clinics with minimal morbidity.

γ-Aminobutyric acid type A receptors (GABAA-Rs) are considered to be the primary molecular targets of injectable anesthetics such as propofol, etomidate and the neurosteriod, alphaxalone. A number of studies have sought to understand the specific GABAA-R subtypes involved in the mechanism of action of these three drugs. Here, we investigated the role of α4-subunit containing GABAA-Rs in the neurobehavioral responses to these drugs. Drug responses in α4 subunit knockout (KO) mice were compared to wild type (WT) littermate controls. While etomidate and propofol are currently used as injectable anesthetics, alphaxalone belongs to the class of neurosteroid drugs having anesthetic effects. Low dose effects of etomidate and alphaxalone were studied using an open field assay. The moderate and high dose effects of all three anesthetics were measured using the rotarod and loss of righting reflex assays, respectively. The locomotor stimulatory effect of alphaxalone was reduced significantly in α4 KO mice compared to WT controls. Neither the low dose sedating effect of etomidate, nor the moderate/high dose effect of any of the drugs differed between genotypes. These results suggest that α4 subunit-containing GABAA-Rs are required for the low dose, locomotor stimulatory effect of alphaxalone but are not required for the sedating effect of etomidate or the moderate/high dose effects of etomidate, propofol or alphaxalone on motor ataxia and loss of righting reflex.

Benzodiazepine treatment can result in dependence as evidenced by signs of withdrawal upon discontinuation of use.Positive GABA(A) receptor modulators were examined for their capacity to attenuate flumazenil-like discriminative stimulus effects (i.e., withdrawal) that emerge upon discontinuation of chronic benzodiazepine treatment.Rhesus monkeys receiving chronic diazepam (5.6 mg(-1) kg(-1) 24 h(-1) p.o.) discriminated flumazenil (0.1 mg/kg s.c.) from vehicle.Upon discontinuation of diazepam treatment, responding switched from the vehicle to the flumazenil lever, although at different times among monkeys. The shorter-acting benzodiazepine lorazepam (3.2 mg(-1) kg(-1) 8 h(-1)) was substituted for diazepam and, 11 h after lorazepam, monkeys consistently responded on the flumazenil lever. Flumazenil-lever responding after acute lorazepam deprivation was attenuated not only by benzodiazepines (lorazepam and midazolam) but also by positive GABA(A) receptor modulators acting at neuroactive steroid (pregnanolone and alfaxalone) and barbiturate sites (pentobarbital). Deprivation-induced responding on the flumazenil lever was not attenuated by low efficacy positive GABA(A) modulators (bretazenil and L-838,417) or non-GABA(A) receptor ligands (ketamine and cocaine). Neuroactive steroids were relatively more potent than other positive GABA(A) receptor modulators in attenuating deprivation-induced flumazenil-lever responding, as compared to their relative potency in monkeys discriminating midazolam and otherwise not receiving benzodiazepine treatment.These results suggest that positive GABA(A) receptor modulators acting at different sites attenuate withdrawal induced by discontinuation of benzodiazepine treatment, consistent with previous studies suggesting that the same compounds attenuate flumazenil-precipitated withdrawal. Differences in the relative potency of positive modulators as a function of acute versus chronic benzodiazepine treatment suggest that neuroactive steroids, in particular, are especially potent in benzodiazepine-dependent animals.

Rationale: Aggressive behavior of certain individual animals can be greatly increased when under the influence of low doses of alcohol. One of alcohol's neurochemical actions that may be relevant to alcohol-heightened aggression (AHA) is its positive modulation of the GABAA receptor complex. Objective: The objective of this study was to investigate whether alcohol interacts with an endogenous modulator of the GABAA receptor complex, the neurosteroid allopregnanolone, in stimulating/heightening aggressive behavior. Methods and results: The first experiment was designed to test the hypothesis that neurosteroid modulators of the GABAA receptor complex will increase aggression and to compare these effects with alcohol. Male CFW mice were injected with allopregnanolone, alphaxalone (3–30 mg/kg, IP), or alcohol (1.0 g/kg, PO) 15 min prior to a 5-min confrontation with an intruder. Moderate doses of alcohol and the neurosteroids increased aggression by ca. 50% above baseline; impaired locomotion was seen only at the highest doses. A second experiment compared AHA and ANA (i.e. alcohol-non-heightened aggression) mice by giving allopregnanolone (1–10 mg/kg) with a simultaneous oral injection of alcohol (0.6 or 1.0 g/kg) or water. When administered with water and the 0.6 g/kg dose of alcohol, allopregnanolone increased the aggression of AHA and ANA mice. Administration of the 1.0 g/kg dose of alcohol in ANA mice prevented allopregnanolone-heightened aggression. In AHA mice, addition of allopregnanolone to 1.0 g/kg alcohol dose-dependently reduced alcohol-heightened aggression, suggesting potentiation of alcohol's suppressive effects on aggression. Conclusions: The neuroactive steroid allopregnanolone appears to play an important role in alcohol-heightened aggression. Moreover, the upward shift of the aggression-heightening effects of alcohol and the downward shift at the maximally effective alcohol dose by allopregnanolone point to a shared mechanism for both positive modulators of the GABAA receptor complex.

γ-AMlNOBUTYRlC acid (GABA), a major inhibitory neurotransmitter in the mammalian nervous system, is known to operate bicuculline-sensitive CI− channels through GABAA receptors and bicuculline-insensitive cation channels through GABAB receptors1,2. Recent observations indicate that the retina may contain GABA receptors with unusual pharmacological properties3–5. Here we report that GABA gates bicuculline-insensitive CI− channels in rod bipolar cells of the rat retina, which were not modulated by flunitrazepam, pentobarbital and alphaxalone and were only slightly blocked by picrotoxinin. Moreover, the GABAB receptor agonist baclofen, and the antagonist 2-hydroxysaclofen had no effect. The underlying single-channel conductance was 7 pS and the open time 150 ms. These values are clearly different from those obtained for GABAA receptor channels recorded in other neurons of the same preparation, and in other parts of the brain1,6–8. The bicuculline- and baclofen-insensitive GABA receptors were activated selectively by the GABA analogue cis-4-aminocrotonic acid (CACA)9. Hence they may be similar to those receptors termed GABAC receptors10.

The non-anaesthetic steroid Δ16-alphaxalone antagonises the depressant action of the anaesthetic steroid alphaxalone on synaptic transmission. This antagonism is not predicted by classical theories of anaesthesia and therefore poses fundamental questions about the molecular basis of anaesthesia.

The use of Althesin for induction of anaesthesia in 57 patients showed that it is a satisfactory induction agent. However, with the exception of rapid recovery with minimal after-effects, it has no major advantages over the commonly used barbiturates.

We have examined four mathematical systems modeling the transit of the steroid anesthetic alphaxalone (3 alpha-hydroxy-5 alpha-pregnane-11,20-dione) through the lung. Using the isolated rat lung perfused with a plasma substitute containing 14C-alphaxalone and 3H-dextran, we have obtained results that are incompatible with models involving (a) anatomical variations in the microcirculation, (b) high solubility, or (c) specific binding. We develop a stochastic model of a physical process analogous to the sequence of events that takes place in a chromatography column. This model closely fits the experimental data and predicts a peak effluent concentration of alphaxalone that may occur after washout with several exclusion volumes. It represents a delay with the pulmonary compartment that may explain a difference in induction times observed between various intravenous anesthetic agents.

General anaesthesia with Althesin was administered on two occasions to a patient who was identified as susceptible to malignant hyperthermia, in whom there was identified familial subclinical myopathy and once in another patient suffering from arthrogryposis multiplex congenita with a history of fever associated with two previous anaesthetics. In the first patient halothane was administered by accident in association with the Althesin, but no hyperpyrexia occurred. In the second instance nitrous oxide-oxygen and halothane were associated purposely with Althesin. In none of these cases was there any rise in temperature, muscle rigor or elevation of the serum CPK level. This experience corroborates the experimental evidence of Hall, et al.10 and Harrison, who reported that Althesin prevented the onset of hyperthermia, and the clinical reports of Page and Judelman. Althesin can be assumed to be an effective anaesthetic for malignant hyperthermia susceptible patients.

Althesin was compared with thiopentone in a double blind study of 200 patients undergoing gynaecological operations. Althesin in a dose of 0.05 ml/kg was found to be an excellent induction agent, virtually devoid of undesirable side effects; however, when used as the principal anaesthetic (supplemented only by 66 per cent nitrous oxide in oxygen), the incidence of disturbing movements was high. Recovery time from Althesin was one-third of that after thiopentone. The patients recovering from Althesin were remarkably clearheaded with a low incidence of "hangover".

Respiratory activity of anaesthetized pigeons was stimulated by occluding the trachea. Inspiratory and expiratory efforts were measured in an early and in the agonal period of prolonged tracheal occlusions.

Electron microscopic studies of the rat hepatocytes reveal that SC-11927 leads to extensive proliferation of the smooth-surfaced endoplasmic reticulum (SER). Treatment with ethylestrenol, oxandrolone or hydroxydione results in a less pronounced increase of the smooth membranes. Progesterone, testosterone, estradiol and the non-steroidal stilbestrol induce only an insignificant increase of the SER. Prednisolone, triamcinolone and DOC do not elicit SER proliferation.

In the rat, deep anaesthesia produced by heavy overdosage with methyprylon can be overcome both by typical catatoxic steroids (ethylestrenol, sc-11927, spironolactone, norbolethone, oxandrolone) and by glucocorticoids (prednisolone, triamcinolone). On the other hand, desoxycorticosterone, progesterone, and hydroxydione, which are devoid of glucocorticoid activity and possess little or no catatoxic potency, fail to offer significant protection against methyprylon.

1. The various effects of neuroleptic, anesthetic and analeptic drugs were studied on the extensor-fusimotor response to pinna stimulation (PS) in decerebrate cats. 2. Chlorpromazine, in contrast to previously observed differential effects of i. v. anesthetics, depressed in a nonspecific manner the facilitatory as well as the inhibitory influences of the PS. This depressant effect of chlorpromazine on the fusimotor-influencing systems of the brain stem was independent of the later occurring fall in blood pressure. 3. Facilitatory PS-responses in decerebrate animals were changed to inhibitory ones by anesthetics. These inhibitory PS-responses were used to test the antagonistic-analeptic effects of bemegride and pentetrazol. 4. Bemegride regularly fully removed the inhibitory PS-response produced by barbiturates (pentobarbital sodium and butallylonal sodium), thus reversing it to facilitation. However, its counteraction against chloralose was only short and incomplete. 5. Pentetrazol also showed a strong antagonistic influence upon the barbiturate-induced alterations of the PS-response, although this was distinctly weaker than that of bemegride. Pentetrazol did not affect the chloralose-induced inhibitory PS-response at all. 6. The PS proved to be a comprehensive, effective and natural procedure to activate the brain stem reticular formation. Its descending fusimotor effects can give conclusive information about the experimentally altered functional condition of these structures. Therefore, the PS-method allows a simple testing of interfering effects of centrally acting drugs.