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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Detomidine, a potent alpha 2-adrenergic receptor agonist, was chosen for study alone and in combination with ketamine with or without diazepam. Four regimens were evaluated: detomidine (150 micrograms/kg of body weight) alone (D); ketamine (35 mg/kg) and detomidine (150 micrograms/kg) (KD); ketamine (35 mg/kg) and high-dose detomidine (300 micrograms/kg) (KDh); and ketamine (35 mg/kg), diazepam (1 mg/kg), and detomidine (150 micrograms/kg) (KDD). The same six rabbits were anesthetized with each combination at weekly intervals. Atropine (0.04 mg/kg) was administered as a preanesthetic 5 min prior to test substance administration. All agents were administered IM, except for diazepam, which was administered IV. Heart and respiratory rates, mean arterial blood pressure, and arterial blood gas tensions were measured. Pedal, palpebral, and righting reflexes also were evaluated. Cardiopulmonary depression, as indicated by decrease in heart and respiratory rates, blood pH, PO2, and increase in PCO2, was observed in all groups. With the exception of heart rate, detomidine used alone caused the least depression of these parameters. Reflexes were consistently lost only after KDh and KDD administrations. The pedal reflex, used as an index of anesthetic depth, was lost in response to KDh and KDD for 56.7 +/- 11.6 and 43.8 +/- 7.4 min, respectively (mean +/- SEM). Three of the six rabbits were anorectic after KDh administration. Necropsy and histologic evaluation revealed myocardial necrosis and fibrosis in five animals. Due to the inconsistent reflex loss in response to KD and D and inappetance associated with KDh, these combinations were not considered safe or reliable.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Evaluation of detomidine anesthetic combinations in the rabbit. 784 56

1. Experiments were carried out to characterize the receptors mediating the indirect excitatory response to 5-hydroxytryptamine (5-HT) in the guinea-pig isolated trachea. 2. 5-HT caused concentration-dependent contractions of tracheal strips, and the resulting concentration-response curve was biphasic in nature. The first phase was obtained with agonist concentrations in the range of 0.01-3 nM and achieved a maximum which was 30% of the total 5-HT response, while the second phase was in the range 10 nM-1 microM. 3. Atropine (0.1 microM) and tetrodotoxin (TTX: 0.3 microM) significantly reduced both phases of the 5-HT curve. Morphine (10 microM), which can act to inhibit neuronal acetylcholine release, abolished the first phase and reduced the second phase. This suggests that the first phase is mainly neurogenic (cholinergic) in nature, while the second phase is in part neurogenic and in part due to direct activation of the effector cells. 4. The 5-HT2A receptor antagonist, ketanserin (0.01, 0.1 microM) markedly depressed the first phase and shifted the second phase to the right in a parallel manner, with some depression of the 5-HT response maximum. The less selective (5-HT1/5-HT2A) antagonist, methiothepin (0.1 microM) mimicked the action of ketanserin, albeit with less potency. Concomitant administration of ketanserin and methiothepin (each at 0.1 microM) produced an antagonism similar to that caused by ketanserin (0.1 microM) alone. 5. The 5-HT3 receptor antagonists, ondansetron (0.1 microM) and granisetron (0.01 microM) slightly but significantly inhibited the first phase of the 5-HT curve without altering the second phase. SDZ 205,557(0.3 MicroM), a 5-HT4 receptor antagonist, was ineffective.6. Our results suggest that neural 5-HT2A and, to a lesser extent, 5-HT3 receptor subtypes mediate the first phase of the 5-HT curve in the guinea-pig trachea. The second phase is mediated by 5-HT2Areceptors, which are probably located at both the neural and muscular level. No evidence for the participation of 5-HT1 receptors in the 5-HT response has been obtained.
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PMID:A pharmacological analysis of receptors mediating the excitatory response to 5-hydroxytryptamine in the guinea-pig isolated trachea. 792

The acute cardiovascular and respiratory effects of poisoning by high soman doses and its therapy by atropine, as well as the underlying mechanisms, are not well known as yet. Therefore, it was the purpose of this study to analyze the circulatory and respiratory functions in soman-poisoned and atropine-treated guinea-pigs. Female Pirbright-white guinea-pigs were anaesthetized with urethane (1.8 g/kg) and the arteria carotis, vena jugularis and trachea were cannulated. After base line measurements, soman (32, 80 or 160 micrograms/kg, i.v.; i.e. 2, 5 or 10 x LD50, respectively) or saline were injected and 2 min later, atropine (10 mg/kg, i.v.) or saline were applied. Respiratory and circulatory parameters were recorded for 60 minutes or until death of the animals. Poisoning by soman resulted in a rapid respiratory arrest, followed by circulatory failure and death after a few minutes. Atropine treatment restored circulatory parameters after soman (2 x LD50) and improved respiration to about 80% of base line values. All animals survived the 60 minutes period. After soman (5 x LD50), atropine improved respiratory parameters only slightly and circulatory parameters markedly. Only 2 of the 8 guinea-pigs survived. Atropine was almost completely ineffective after soman (10 x LD50), despite of a transitory improvement of circulation, and all animals died within a few minutes. In control animals, atropine did not impair respiration or circulation. The results of this study suggest that the soman-induced respiratory depression is primarily caused at the central nervous level and that a significant peripheral neuromuscular block develops only at very high soman doses. The circulatory disturbances are mainly the result of bradycardia due to peripheral muscarinic stimulation. Atropine has a high therapeutic effect in the restoration of circulatory function and may even improve respiration at high soman doses.
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PMID:Analysis of cardiovascular and respiratory effects of various doses of soman in guinea-pigs: efficacy of atropine treatment. 811 34

1. The negative inotropic effects of soman have been reported previously. It was suggested that the depression in atrial force of contraction was a consequence of continuous muscarinic receptor activation by excessive acetylcholine (ACh) accumulation and also possibly through direct interactions at the receptor-associated K+ channels by organophosphate (OP). 2. In this study, the protective effects of tacrine (THA), an antimuscarinic as well as a K+ channel blocker, against soman in guinea-pig atrium were investigated. 3. It was found that tacrine could antagonize the negative inotropic effects of soman. This antagonism occurred in a concentration dependent manner, with effective concentrations (ECs) for tacrine ranging from 1.7 to 12.1 microM when the atrium was equilibrated with 0.05-10 microM soman. 4. Inclusion of an oxime HI-6 (100 microM) in the regimen improved the efficacy of tacrine against soman (1 microM) by 16.1 fold. 5. Addition of a potent antimuscarinic, either atropine or glycopyrrolate with tacrine also improved tacrine's efficacy against soman significantly. 6. Atropine, at equivalent concentration, appeared to be the most effective of the three. At 0.1 microM concentration, atropine was 4.25 and 3.47 times more potent than HI-6 and glycopyrrolate respectively in enhancing THA efficacy. 7. Our results suggested that the immediate suppression of the muscarinic manifestations and the reactivation of the enzyme acetylcholinesterase for the removal of excess ACh are both critical in maintaining the mechanical functions of a heart during acute OP poisoning. The blockade of K+ channels by tacrine may also contribute to countering the depressant effects of soman.
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PMID:Protection by tacrine and some adjuncts against the depressant effects of soman in guinea-pig atrium. 811 29

The effects of cold and restraint and of some of the antiulcer drugs on adenosine nucleotide content in the gastric glandular mucosa were examined. A bioluminescence technique was used to measure the amount of ATP and its metabolites in gastric mucosal tissue. Cold-restraint produced gastric lesions and increased the gastric mucosal ATP. Verapamil pretreatment attenuated these lesions and further intensified the ATP increase in a dose-related manner. The ATP/ADP ratio and the Atkinson index were also elevated. Calcium gluconate produced similar effects. Atropine or EGTA pretreatment protected or worsened the gastric lesion, respectively, but did not have any influence on the changes in mucosal energy metabolism. Ranitidine pretreatment lessened the lesion formation but had no influence on the nucleotide content. These findings indicate that the metabolic rate of the gastric mucosa is suppressed during cold-restraint conditions; this depression is probably due to hypothermia and reduction of mucosal metabolism. The lesion-protecting mechanisms of the drugs do not seem to be mediated through their effects on mucosal energy metabolism. The oxygen- and ATP-sparing effects of verapamil may contribute partly to its gastro-protective effect.
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PMID:Role of gastric glandular mucosal energy metabolism in cold-restraint gastric lesion formation. 818 16

The action of sarin, an organophosphorus (OP) compound, was examined in vitro for its effects on the spinal monosynaptic reflex (MSR) in neonatal rats. The effects of sarin were biphasic, i.e. facilitation at lower concentrations (2-20 nM) followed by depression of the MSR at concentrations above 30 nM. Facilitation of MSR was maximal (150% of control) at 20 nM sarin. The depression of MSR was maximal (70% of control) at 200 nM sarin, with half maximal inhibition occurring at 90 nM sarin. Atropine (200-500 nM) effectively reversed the depression caused by sarin, while pretreatment with low concentrations of atropine (10 nM) completely blocked the depression otherwise observed with sarin. Benactyzine was also effective in preventing sarin-induced depression, while pirenzepine was less effective. The nicotinic blocking agents tubocurarine and mecamylamine were, however, ineffective in preventing or reversing sarin-induced depression. The facilitation of MSR seen with lower concentrations (2-20 nM) correlated well with the blockade of late phase inhibition (between 30 and 50 ms conditioning-test interval) elicited in spinal cord by stimulating the adjacent dorsal root at various condition-test intervals, which has been shown elsewhere to be sensitive to bicuculline (Deshpande and Warnick 1988). Thus it is speculated that sarin at lower concentrations blocks GABA transmission, producing facilitation, and at higher concentrations activates the muscarinic receptors producing depression of MSR. The beneficial action of pretreatment with antimuscarinic agents may be attributed to the protection of the muscarinic receptors.
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PMID:Biphasic action of sarin on monosynaptic reflex in the neonatal rat spinal cord in vitro. 836 39

1. Conventional microelectrode techniques were used for intracellular recordings of the transmembrane electrical potentials, the effects of berberine were studied on canine cardiac Purkinje and ventricular muscle fibres and on rabbit atrial fibres. 2. Berberine (3-30 microM) increased in a concentration-dependent manner, the action potential duration (APD) in canine Purkinje and ventricular muscle without affecting other parameters of the action potential. 3. The berberine-induced enlargement of the APD showed reverse use-dependence, so that the effect was greater at lower rates of stimulation. 4. Preparations perfused with berberine (30 microM) and driven at rates below 0.5 Hz exhibited early after depolarizations which persisted 3-4 h after washing. 5. The early afterdepolarizations were reversibly abolished by perfusion with lignocaine (3 microM) or by the increase in the rate of stimulation. 6. The effective refractory period (ERP) of Purkinje fibres was greatly increased by berberine (30 microM); however, the ratio ERP/APD was not significantly affected. 7. Berberine (10-100 microM) decreased in a concentration-dependent manner the spontaneous frequency of rabbit sinoatrial cells. The decrease in frequency was accompanied by a depression of the phase 4 depolarization, without significant changes in other parameters of the nodal action potential. 8. Atropine (2.5 microM) did not affect the bradycardic effect of berberine. On the other hand, berberine (30 microM) did not alter the chronotropic effect of isoprenaline. 9. Berberine (30 microM) also increased the duration of slow responses in K-depolarized rabbit atrial muscle fibres, other parameters being unaffected. 10. It is suggested that berberine exerts Class III antiarrhythmic and proarrhythmic actions in cardiac muscle of the dog in vitro.
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PMID:Electropharmacological effects of berberine on canine cardiac Purkinje fibres and ventricular muscle and atrial muscle of the rabbit. 844

Using electrophysiological techniques in the in vitro rat auditory cortex, we have examined how spontaneous acetylcholine (ACh) release modifies synaptic potentials mediated by glutamate and gamma-aminobutyric acid (GABA). Single stimulus pulses to lower layer VI elicited in layer III a four-component (A-D) extracellular field response involving synaptic potentials mediated by glutamate and GABA. The cholinesterases inhibitor eserine (10-20 microM) or the cholinergic agonist carbachol (25-50 microM) depressed by 10-50% the glutamatergic components A and C, and the GABAergic components B and D. Atropine reversed the depressive effects of eserine and carbachol. A novel finding was that the degree of depression of component A varied inversely with stimulus intensity. However, during partial pharmacological antagonism of GABAA receptors, depression of A varied directly, not inversely, with stimulus intensity. Normally, then, depression of A is offset by reduced GABAergic inhibition of A. We also tested for differential depression of responses mediated by N-methyl-D-aspartate (NMDA) versus non-NMDA glutamate receptors. Following physiological and pharmacological isolation of the responses, eserine depressed the non-NMDA, but not the NMDA, receptor-mediated potential. Since the isolated NMDA potential still could be depressed by carbachol, the data suggested that activation of NMDA receptors may reduce spontaneous ACh release. In support of this, preincubation of slices in NMDA (10-20 microM) largely prevented eserine's, but not carbachol's, depression of components A and B. These results permit three conclusions of relevance to cortical information processing: (1) spontaneous ACh release tonically depresses synaptic potentials mediated by glutamate and GABA; (2) ACh depresses responses to weak inputs to a greater degree than responses to strong inputs: (3) activation of NMDA receptors may "feedback" to reduce ACh release, a mechanism that could place regulation of local ACh release under glutamatergic afferent control.
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PMID:Synaptic interactions involving acetylcholine, glutamate, and GABA in rat auditory cortex. 875 Oct 63

Our study investigated the effects of moderate doses of fentanyl and sufentanil versus high-dose sufentanil on cerebral hemodynamics by using transcranial Doppler ultrasonography (TCD). Thirty American Society of Anesthesiologists (ASA) II and III patients scheduled for elective coronary artery bypass graft (CABG) were studied after Institutional Review Board (IRB) approval and informed consent. The evening before surgery, all patients received oral flurazepam (1 mg/kg), Atropine (0.4 mg/70 kg s.c.) and a combination of droperidol (70 micrograms/kg s.c.) plus fentanyl (1.5 micrograms/kg s.c.) were given as preanesthetic medication 1 h before induction of anesthesia. Anesthesia was induced with either 25 micrograms/kg fentanyl i.v. (group 1, n = 10), 3 micrograms/kg sufentanil i.v. (group 2, n = 10) or 6 micrograms/kg sufentanil i.v. (group 3, n = 10). All patients received 100 micrograms/kg pancuronium i.v. With the induction of respiratory depression, assisted ventilation was performed followed by controlled ventilation to maintain normoxia and normocapnia (FiO2, 1.0). Cerebral blood flow velocity (CBFV, cm/s) was measured continuously in the middle cerebral artery by using a bidirectional 2-MHz TCD system. Monitoring included heart rate (HR, beats/min), direct mean arterial blood pressure (MAP, mm Hg), and PaCO2. Physiologic variables including arterial blood gases were measured at baseline, 5 min, and 10 min after infusion of fentanyl or sufentanil. In all patients, HR, MAP, end-tidal carbon dioxide tension (PetCO2), and PaCO2 were constant over time and did not differ between groups. CBFV did not change with moderate doses of fentanyl (group 1) or sufentanil (group 2). In contrast, infusion of high-dose sufentanil (group 3) was associated with 27 to 30% decreases in CBFV (p < 0.05). Our results suggest that sufentanil decreases CBFV in a dose-related fashion with a threshold effect. Increases in CBFV and CBF seen in previous studies may be related to an increasing PaCO2 when maintenance of normocarbia is based on only real-time capnography with a constant PetCo2 rather than additional arterial blood gas monitoring.
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PMID:The effects of fentanyl and sufentanil on cerebral hemodynamics. 923 83

1. Acetylcholine causes a rise of intracellular Ca2+ in perisynaptic Schwann cells (PSCs) of the frog neuromuscular junction. The signalling pathway was characterized using the fluorescent Ca2+ indicator fluo-3 and fluorescence microscopy. 2. Nicotinic antagonists had no effect on Ca2+ responses evoked by ACh and no Ca2+ responses were evoked with the nicotinic agonist nicotine. The muscarinic agonists muscarine and oxotremorine-M induced Ca2+ signals in PSCs. 3. Ca2+ responses remained unchanged when extracellular Ca2+ was removed, indicating that they are due to the release of Ca2+ from internal stores. Incubation with pertussis toxin did not alter the Ca2+ signals induced by muscarine, but did block depression of transmitter release induced by adenosine and prevented Ca2+ responses in PSCs induced by adenosine. 4. The general muscarinic antagonists atropine, quinuclidinyl benzilate and N-methyl-scopolamine failed to block Ca2+ responses to muscarinic agonists. Atropine (at 20,000-fold excess concentration) also failed to reduce the proportion of cells responding to a threshold muscarine concentration sufficient to cause responses in less than 50% of cells. Only the allosteric, non-specific blocker, gallamine (1-10 microM) was effective in blocking muscarine-induced Ca2+ responses. 5. In preparations denervated 7 days prior to experiments, low concentrations of atropine reversibly and completely blocked Ca2+ responses to muscarine. 6. The lack of blockade by general muscarinic antagonists in innervated, in situ preparations suggests that muscarinic Ca2+ responses at PSCs are not mediated by any of the five known muscarinic receptors or that post-translational modification prevented antagonist binding.
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PMID:Muscarinic Ca2+ responses resistant to muscarinic antagonists at perisynaptic Schwann cells of the frog neuromuscular junction. 936 8


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