Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. The effects of sodium pentobarbital and alpha-chloralose anesthesia on the baroreflex control of circulation were studied in groups of 7 to 11 rats. The tests were performed in conscious undisturbed rats and repeated after anesthesia. 2. Pentobarbital (15 min) depressed the initial peak of the pressor response produced by carotid occlusion by 68% (15 +/- 1 vs 47 +/- 3 mmHg) and the maintained response by 52% (13 +/- 1 vs 27 +/- 4). Depression by chloralose was 48% (26 +/- 5 vs 50 +/- 3) and 21% (19 +/- 2 vs 24 +/- 3), respectively. The inhibition progressively declined at 30, 60, 90 and 120 min after pentobarbital but was unchanged up to 120 min after chloralose. 3. The baroreflex sensitivity index for bradycardic responses (phenylephrine injection) diminished by 50% after pentobarbital (-1.1 +/- 0.3 vs -2.2 +/- 0.3 beats/min per mmHg) and remained unaltered after chloralose. 4. The baroreflex sensitivity index for tachycardic responses (nitroprusside injection) was depressed by 61% after pentobarbital (-1.5 +/- 0.5 vs -3.8 +/- 0.5 beats/min per mmHg) and 35% after chloralose (-2.5 +/- 0.2 vs -3.9 +/- 0.5). 5. In general the depression of reflex control of circulation was more severe after pentobarbital than after chloralose anesthesia, while the resting control arterial pressure was not affected by either. The inhibition of the baroreflex tachycardic responses was more intense than that of the bradycardic responses and represented a better index of the depression exerted on the pressure responses to carotid occlusion.
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PMID:Influence of general anesthetics on baroreflex control of circulation. 213 30

New planar lipid bilayer technology enabled the pharmacologic study of single sodium channels from human brain, overcoming the limitations of tissue availability and the rapid loss of protein function in conventional experimental preparations. Synaptosomal vesicles prepared from human brain cortical tissue were fused with planar lipid bilayers. In the presence of batrachotoxin, sodium channels were incorporated into lipid bilayers and their single-channel properties studied. Pentobarbital was found to depress two major functions of the sodium channel, leading to a voltage-independent reduction of the fractional channel open-time (ED50 0.61-0.75 mM) and an interaction with the voltage-dependent steady-state activation. The steady-state activation curve was shifted to more negative potentials and had a reduced slope, i.e., negative membrane potentials became less effective at closing sodium channels. The results were consistent with a pentobarbital-induced increase in protein flexibility. The actions of the two optical stereoisomers of pentobarbital showed no significant differences, indicating that other ion channels must also be involved in the clinical actions of barbiturates. The pentobarbital effects on sodium channels occurred at concentrations thought to be relevant in general anesthesia and within the clinical range. This suggests that sodium channels could contribute to overall anesthetic depression, supporting our hypothesis that anesthesia results from the superposition and integration of several anesthetic actions at the molecular level.
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PMID:Molecular actions of pentobarbital isomers on sodium channels from human brain cortex. 215 52

Effects of pentobarbital on the calcium current of Aplysia neurons were investigated under current- and voltage-clamp conditions using the conventional two-microelectrode technique. Pentobarbital attenuated the progressive broadening of repeated action potentials of somata, suggesting a reduction in the calcium current. When calcium ion was replaced with barium ion in the perfusing solution, in which neither sodium nor potassium ions carried transmembrane currents, the barium current (IBa) which flowed through the calcium channel of the cell membrane was generated by depolarizing pulses of several hundred milliseconds applied every 1 min from a holding potential of -50 mV. The IBa was not affected by tetrodotoxin (30 microM). The current was decreased by pentobarbital (0.1-5 mM) in a dose-dependent manner. The inhibition was much greater at a lower pH of the perfusate, indicating that the uncharged form of the agent was responsible. The voltage-dependent inactivation of the IBa proceeded with two time constants [190 +/- 21 and 2020 +/- 146 msec (N = 4) at -10 mV], both of which were shortened by adding 1 mM pentobarbital [to 120 +/- 18 and 540 +/- 51 msec (N = 4), respectively]. The IBa recovered from the inactivation with two time constants [60 +/- 7 and 871 +/- 76 msec (N = 3) at -50 mV]. The anesthetic (1 mM) prolonged both of them, to 124 +/- 20 and 1480 +/- 172 msec (N = 3), respectively, resulting in a use-dependent depression of the current at 2-Hz stimulation. Pentobarbital reduced the IBa to a greater extent when the holding potential was more positive (-30 instead of -50 mV), indicating a higher affinity of the drug to the inactivated state of the channel. These findings suggest that the attenuation of the progressive broadening of successive spikes by pentobarbital is due to a decrease in the voltage- and time-dependent calcium current, ending in depression of transmitter release from the nerve terminal.
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PMID:Reduction of the voltage-dependent calcium current in Aplysia neurons by pentobarbital. 243 43

In order to determine the possible involvement of GABA-ergic mechanisms in the modulation of the cough reflex, the effects of GABA antagonists on the pentobarbital-induced depression of respiration and cough were examined in a comparative study in rats. The cough reflex was induced by application of electrical stimulation to the tracheal mucosa by the puncture electrode-induced cough method. The 50% antitussive dose (AtD50) of pentobarbital was calculated by the "up and down" method. Pentobarbital (10 mg/kg, IP) caused a reduction of tidal volume, which was counteracted by pretreatment with picrotoxin (3 mg/kg, IP) or bicuculline (3 mg/kg, IP). However, neither picrotoxin nor bicuculline were able to counteract the reduction in frequency of respiration. The AtD50 of pentobarbital was 1.95 mg/kg when administered IP. The AtD50 of pentobarbital was not altered after pretreatment of rats with picrotoxin (1.85 mg/kg, IP) or with bicuculline (1.55 mg/kg). These results suggest that GABA-ergic mechanisms may not be involved in the cough-depressant effect of pentobarbital.
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PMID:Effects of GABA antagonists on the pentobarbital-induced depression of respiration and cough in rats. 254 92

The state of deep surgical anaesthesia, induced by intraperitoneal injection of pentobarbital sodium (54 mg/kg) or ketamine hydrochloride (150 mg/kg) in the rat, was accompanied by a significant reduction in the permeability of the blood-brain barrier evaluated by calculating a unidirectional blood-to-brain constant (Ki) for the circulating tracer [14C]alpha-aminoisobutyric acid. Pentobarbital-induced anaesthesia was also characterized by a widespread and marked depression of local cerebral glucose utilization; on the contrary, when rats were anaesthetized with ketamine, cerebral glucose utilization increased in the striatum and hippocampus and decreased in the cerebellum and brain-stem. It is suggested, as a hypothesis, that two different mechanisms, depending on the kind of the anaesthetic drug used, may be involved in the changes in the permeability of the blood-brain barrier, observed in anaesthetized animals: (a) a neurogenic component; (b) a direct interaction of the anaesthetic with elements of the microvasculature.
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PMID:Modifications of the permeability of the blood-brain barrier and local cerebral metabolism in pentobarbital- and ketamine-anaesthetized rats. 281 89

It has been reported that pentobarbital facilities binding to benzodiazepine receptors binding at anesthetic concentrations and that this action may play a role in the anesthetic potency of this barbiturate. The interaction between pentobarbital and benzodiazepine receptors was tested with Ro 15-1788 which is reported to be a pure benzodiazepine antagonist and 3-hydroxymethyl-beta-carboline (3-HMC), an antagonist which has inverse activity alone. Cerebral blood flow (CBF) and cerebral oxygen consumption (CMRO2) were measured in rats after injections of pentobarbital with and without the antagonists. Pentobarbital produced dose-dependent decreases in cerebral blood flow and cerebral oxygen consumption at 15 and 30 mg/kg. The antagonist Ro 15-1788 (10 mg/kg) stimulated cerebral blood flow and cerebral oxygen consumption alone but did not alter the cerebral depression produced by pentobarbital. The cerebral metabolic stimulation produced by Ro 15-1788 was unexpected since the drug is reported to be a pure antagonist without agonistic activity, but the lack of effect on pentobarbital-induced cerebral depression is consistent with other reports. 3-Hydroxymethyl-beta-carboline at 10 mg/kg did not stimulate cerebral blood flow and cerebral oxygen consumption but significantly antagonized the decrease in cerebral oxygen consumption produced by 15 mg/kg pentobarbital. 3-Hydroxymethyl-beta-carboline had no significant effect on decreases in cerebral blood flow and cerebral oxygen consumption produced by phenobarbital, a barbiturate which is reported not to alter binding to benzodiazepine receptors. The ability of 3-HMC to antagonize the effects of pentobarbital would be consistent with an action of both drugs at the benzodiazepine receptor but not by altering binding to an endogenous receptor.
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PMID:The interaction between benzodiazepine antagonists and barbiturate-induced cerebrovascular and cerebral metabolic depression. 299 34

The present study investigated the effect of systemically administered pentobarbital on the tail-flick (TF) reflex in rats, the neurochemical mechanism of action and the role of descending influences. Pentobarbital produced a clear inhibition of the TF response. Systemic administration of naloxone did not significantly alter this effect, thus it appears to be independent of endogenous opioid systems. Complete spinal transection resulted in a marked potentiation of pentobarbital-induced TF inhibition, demonstrating a spinal locus of action. Moreover, this observation suggests the existence of a tonic descending excitatory influence, opposing the pentobarbital-produced depression of nociceptive transmission in the intact animal. Intrathecal administration of pentobarbital caused a much more pronounced TF inhibition in transected than in intact animals, lending further support to this hypothesis. To identify the neurochemical mechanisms involved in pentobarbital-produced antinociception, the gamma-aminobutyric acid (GABA) antagonists bicuculline and picrotoxinin were administered intrathecally in spinalized animals. Both substances caused an attenuation of the pentobarbital effect, demonstrating the involvement of GABAergic transmission. The proposed descending excitatory system may act either presynaptically and cause a decreased release of GABA into the synapse or postsynaptically via endogenous GABA antagonistic neurotransmitters, which may change the conformation of the GABA-barbiturate receptor complex.
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PMID:Barbiturate-induced inhibition of a spinal nociceptive reflex: role of GABA mechanisms and descending modulation. 303 63

Barbiturate actions on excitatory synaptic responses in CA 1 and dentate regions of hippocampal slices were studied to determine whether different effects occur on anatomically distinct synaptic pathways. Pentobarbital facilitated transmission between stratum radiatum inputs and CA 1 neurons at low concentrations (0.02-0.08 mM) and produced postsynaptic depression at higher concentrations. Only depression was observed for stratum oriens inputs to CA 1 and perforant path inputs to dentate granulae neurons. The (+) isomer of pentobarbital was approximately four times more potent than the (-) isomer of racemic mixture. Phenobarbital (0.04-0.12 mM) produced only depression of synaptic responses in CA 1 and dentate pathways. Comparison of effect on field excitatory postsynaptic potentials and population spike responses indicated that the barbiturates act at selective and pathway-specific sites. The results provide further evidence for specific cellular and membrane recognition sites for barbiturate action.
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PMID:Barbiturate effects on hippocampal excitatory synaptic responses are selective and pathway specific. 303 90

Extracellular single unit recordings were made in the brain stem reticular formation (RF) of urethane-anesthetized rats. Minaprine (cumulative i.v. dose of 10 mg/kg, given as 2.5, 2.5 and 5 mg/kg) has no significant effects on the RF neurons. Pentobarbital (10 mg/kg, i.v.) and scopolamine (5 mg/kg, i.v.) reduced the firing rate of the RF neurons. Minaprine (cumulative i.v. dose of 10 mg/kg, given as 2.5, 2.5 and 5 mg/kg) reversed the effects of pentobarbital and scopolamine. These observations indicate that minaprine has an ameliorating effect on the drug-induced depression of neuronal activity in the RF.
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PMID:Effect of minaprine on neuronal activity in the brain stem reticular formation of the rat. 324 20

A method is described for the measurement of cardiac output and oxygen saturation in closed-chest rats using a small (2.4 F) commercially available fiberoptic catheter and a reflection-spectral-photometer. Positioned in the aortic arch, the catheter functions as an oxymeter for oxygen saturation and as a densitometer for measurement of indocyanine green, obviating the need for blood removal and passage through a densitometer. The sensitivity and reproducibility of this method were characterized in 90 rats by thermodilution, radiolabeled microspheres, and electromagnetic flow methods as standard references. Basal cardiac output as well as changes in cardiac output during isoproterenol infusion and blood removal and replacement were measured. In addition, multiple measurements of cardiac output over 1 min were used to document the method's suitability in constructing a ventricular function curve. With the fiberoptic catheter, cardiac output varied predictably with anesthesia, with rats on dial-urethane (n = 23) having values of 150 +/- 39 (SD) ml/min/kg and 2 and 1% enflurane (18-35 rats per group) yielding cardiac outputs of 190 +/- 60 and 236 +/- 77 ml/min/kg, respectively. Pentobarbital produced the least cardiovascular depression (n = 15) with an average cardiac output of 322 +/- 22 ml/min/kg. The average cardiac output with this method in 90 rats (regardless of anesthesia) was 214 +/- 91 (SD). This value was comparable to cardiac output values determined in paired experiments from radiolabeled microspheres (9 rats) 220 +/- 43, electromagnetic flow (11 rats) 177 +/- 33, and a subset of rats with thermodilution (231 +/- 45 ml/min/kg). The within measurement (repeat measurements) variability with the fiberoptic method was consistently less than the rat-to-rat variability when compared to the thermal and radiolabeled microsphere methods, but it was comparable to electromagnetic flow. The method can be used when rapid measurements (4 measurements within 60 s) of cardiac output are required, as in constructing a ventricular function curve, and can readily detect small changes in cardiac output during controlled hemorrhage and isoproterenol infusion. In summary, this method gives measurement of oxygen saturation and cardiac output by dye dilution without blood removal. There is less surgical preparation than required for electromagnetic cardiac output, and it is an alternative to the thermodilution method.
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PMID:Measurement of cardiac output in anesthetized rats by dye dilution using a fiberoptic catheter. 330 43


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