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

U-78875 (3-(5-cyclopropyl-1,2,4-oxadiazol-3-yl)-5-(1-methylethyl) imidazo[1,5-a]-quinoxalin-4(5H)-one) is a chemically novel compound with a high affinity for the benzodiazepine receptors. It has anticonflict effects in both the Vogel and Cook-Davidson models of anxiety, with a potency similar to that of diazepam (1-3 mg/kg, i.p.). In unanesthetized rats implanted with cortical electrodes for EEG recording, i.p. injections of U-78875 (3-10 mg/kg) increased the EEG power density in frequencies above 12 Hz, and decreased EEG power at lower frequencies. This EEG effect is similar to that of diazepam, and was completely antagonized by pretreatment with flumazenil. In animal models measuring central nervous system depression, U-78875 is much weaker than diazepam. It produced minimal impairment of rotarod performance in rats at doses up to 30 mg/kg, but at lower doses completely reversed the impairment from 10 mg/kg of diazepam. In rats trained to avoid shocks in a shuttle box, U-78875 (3-10 mg/kg) increased avoidance responses and antagonized the suppression of avoidance from diazepam (10 mg/kg). In the mouse one-trial passive avoidance task, pretreatment with U-78875 (1-10 mg/kg) before training produced no anterograde amnesia, but completely blocked the amnesic effect from diazepam (10 mg/kg). The diazepam antagonist potency for U-78875 is 10 to 100 times that of flumazenil. This unusual profile of mixed agonist/antagonist activities suggests U-78875 to be a unique anxiolytic agent with a minimum of central nervous system depression.
 ...
PMID:Behavioral effects of U-78875, a quinoxalinone anxiolytic with potent benzodiazepine antagonist activity. 168 Oct 85

We have studied the effect of i.v. flumazenil 0.01 mg kg-1 on the amnesia and sedation caused by midazolam 2 mg and 5 mg i.v. in volunteers in order to determine the relationship between the actions of the antagonist on these two effects. Midazolam caused dose-dependent central neural depression as assessed by critical flicker fusion frequency, and dose-dependent amnesia for word cards. In subjects given flumazenil 5 min after administration of midazolam, fusion frequency readings and memory were restored to levels comparable to those before midazolam administration. These two effects of flumazenil were similar in time course and extent, suggesting that they share the same mechanism of action. Flumazenil given alone had no effect on memory. The study has demonstrated anterograde amnesia following benzodiazepine administration and antagonism by flumazenil. There was neither retrograde amnesia nor retrograde antagonism of amnesia.
 ...
PMID:Effect of flumazenil on midazolam-induced amnesia. 222 35

A new technique of sedation for children is described, in which midazolam (0.2 mg.kg-1) was administered topically by the nasal route, followed by ketamine (9.0 mg.kg-1) administered rectally in 32 patients breathing air spontaneously. Sedation was good in 23, seven required further ketamine (1.0 mg.kg-1 i.v.), and in two, halothane was introduced. There was no evidence of severe respiratory depression except during oesophagoscopy. Cardiovascular stability was excellent. Of 21 patients over 5 years old, 19 developed complete and two partial anterograde amnesia for the administration of ketamine and surgery. The major complications were nausea and vomiting (five patients) and salivation (eight patients). The mean recovery time was 40 min (s.d. 33 min). It provided a relatively safe, adaptable, non-invasive method of inducing sedation in children.
 ...
PMID:The use of midazolam in diagnostic and short surgical procedures in children. 232 26

Vasopressin may be involved in normal memory functions and may alleviate certain memory impairments. In this study, the usefulness of vasopressin to relieve electroconvulsive therapy (ECT)-induced memory impairment was evaluated using a placebo-controlled, random assignment, double-blind design. Patients were 33 depressives receiving bilateral ECT. Vasopressin, in a nasal spray, was administered q.i.d. from the first through the fifth ECT. Extensive memory testing evaluated both retrograde and anterograde amnesia; ratings of depression and patient ratings of subjective memory complaints were also obtained. Results did not show statistically significant evidence of benefit from vasopressin, though a number of comparisons were in the predicted direction. The role of vasopressin in reducing memory impairment of various types remains to be elucidated.
 ...
PMID:A placebo-controlled evaluation of vasopressin for ECT-induced memory impairment. 240 15

Anesthetic premedication by injection is usually poorly accepted by children, especially those under 10 years of age. Less disturbing for the child is oral premedication, but this increases the risk of aspiration and must be administered 1.5-2 h before anesthetic induction. This double-blind study was performed in children to investigate the efficacy, acceptance, and general safety of midazolam given rectally. METHOD. Rectal premedication was administered to a total of 80 healthy children between 2 and 10 years of age undergoing elective operations. The children were divided randomly into two groups: group I received 0.4 mg/kg and group II 0.5 mg/kg midazolam with the addition of 0.015-0.02 mg/kg atropine. Premedication was carried out on the pediatric ward. The calculated dose was drawn from the ampule and diluted to 8-10 ml with distilled water. This dose was instilled immediately behind the anal sphincter using a suitable plastic applicator (Stanylan). The following parameters were recorded: immediate reaction to the rectal medication, sedative-hypnotic signs, and acceptance of the anesthetic mask. Heart rate and blood pressure were measured before premedication and before the induction of anesthesia. Observations were made for 5 h post-operatively. Any unusual side effects of the treatment were also noted. The existence of any anterograde amnesia was investigated in 20 children (10 in each group) between 6 and 10 years of age. RESULTS. There was no significant difference between the children allocated to the two groups with regard to age, body weight, sex, type of operation, and duration of anesthesia (Table 2). Of the total of 80 children, 66 (82.5%) accepted the rectal instillation well, 12 (15%) moderately well, and 2 (2.5%) poorly. Signs of respiratory depression or allergic reaction to midazolam were not observed in any case. The observations made before induction of anesthesia are presented in Table 3. The children in group II exhibited significantly greater (P less than 0.05) slurred speech than those in group I. A low incidence of hiccup was seen in both groups. Most of the children (27 in group I, 67.5%; 37 in group II, 92.5%: P less than 0.05) were delivered to the operating room lying down, whereas the others were sitting up in bed but showed no desire to get up. Between 10 and 55 min after the premedication, a total of 5 children (12.5%) in group I and 2 (5%) in group II were restless or crying on arrival in the induction room. Most, however, were quiet to tired/drowsy. The optimal sedative-hypnotic action was observed after 20-30 min (Fig. 1). At this time 21.7% of the children in group I were tired/drowsy, whereas 50% in group II were tired/drowsy and 9.1% were asleep but easy to arouse. This effect was significantly greater in group II (P less than 0.01). Acceptance of the mask was comparable in both groups (Table 4) and was tolerated well to very well by 92-97% of the children. (ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:[Rectal premedication with midazolam in children. A comparative clinical study]. 264 8

The technique of in vitro fertilization (IVF) was simplified by the development of ultrasound-supported transvaginal follicular centesis. This makes it possible to dispense with general anesthesia. As an alternative, an intravenous analgosedation with midazolam (0.1 mg/kg) and fentanyl (2 micrograms/kg) is presented. Besides a good analgesic and anxiolytic action, an incipient respiratory depression was observed, so that insufflation of oxygen-enriched air is to be recommended. The operation is felt to be comfortable by almost all patients. A high degree of anterograde amnesia is attained. Meticulous intraoperative and postoperative anesthesiological monitoring is a prerequisite for application of this procedure.
 ...
PMID:[Analgosedation with midazolam and fentanyl as an alternative to general anesthesia in transvaginal follicle puncture within the scope of in vitro fertilization]. 265 73

Midazolam is a 1,4-benzodiazepine derivative with a unique chemical structure: depending on environmental pH, the drug can produce highly water-soluble salts (pH less than 4) or exist in lipophilic diazepine ring-closed form (pH greater than 4). This characteristic contributes to rapid onset of action and to good local tolerance after parenteral administration. After both oral and parenteral administration, midazolam has a fast absorption rate and is rapidly excreted, with a half-life of only about 2 hours. A reasonably good correlation has been found between plasma levels and clinical effects, indicating a fast but brief response. As a hypnotic, midazolam is mainly indicated in insomniac patients with difficulties in falling asleep or having a pathologic sleep pattern during the first half of the night. No marked hangover effects are present the next morning. In anesthesiology, midazolam appears to be a useful, short-acting, sedative-anxiolytic and amnesic premedicant after both oral and parenteral administration. In minor surgery, however, the slow, unpredictable onset and variable duration of action, as compared with thiopental, may inhibit its routine use as an induction agent, especially in young patients, without heavy premedication. In major surgery, midazolam is an alternative to thiopental for induction of anesthesia in spite of its slow, variable induction time. Its advantages include good cardiovascular stability, transient and mild respiratory depression, low frequency of venous irritation, production of anterograde amnesia and short duration of action in comparison with other benzodiazepines.
 ...
PMID:Midazolam: the first water-soluble benzodiazepine. Pharmacology, pharmacokinetics and efficacy in insomnia and anesthesia. 316 Oct 5

Brain cholinergic systems are thought to play an important role in memory function and mood regulation. Electroconvulsive therapy (ECT) and lithium (Li) have substantial therapeutic effects on abnormal mood and may adversely affect cognitive processes. The effects of chronic electroconvulsive shock (ECS) and Li administration on brain muscarinic cholinergic receptors (MCR), and on functional correlates of altered brain cholinergic activity, were therefore studied. ECS reduced MCR number in the cerebral cortex and diminished cataleptic responses to the muscarinic agonist, pilocarpine. MCR down-regulation may have therapeutic implications in depression which has been putatively linked to central cholinergic supersensitivity. Alternatively, ECS effects on brain cholinergic function may be involved in the pathogenesis of ECT-induced memory deficits. Both ECS-induced MCR subsensitivity and a clinically equivalent model of ECT-induced anterograde amnesia were not demonstrable after a single ECS, were cumulatively induced by repeated treatments, and may be reversible by administration concurrently with ECS of a muscarinic antagonist. Li increased MCR binding marginally in the cortex and hippocampus and significantly in the corpus striatum. Li substantially enhanced cataleptic and hypothermic responses to pilocarpine. Combined Li-scopolamine pretreatment had an additive effect on these cholinergically mediated responses. Effects of Li and scopolamine on MCR binding were not additive, a finding supporting the conclusion that Li enhances brain cholinergic function by its presynaptic effects on acetylcholine turnover and release. Possible implications for the therapeutic mechanisms and adverse effects of Li are considered.
 ...
PMID:Studies on the role of brain cholinergic systems in the therapeutic mechanisms and adverse effects of ECT and lithium. 391 9

As a preanesthetic medication, lorazepam is available for oral, intravenous, or intramuscular administration. A parenteral dose of 0.04 to 0.06 mg per kg has been shown to be most effective as a preanesthetic medication in terms of antianxiety and antirecall effect (Table 1). Lorazepam has as its predominant advantage over other benzodiazepines the ability to produce anterograde amnesia reliably and for a relatively long duration. From an anesthesia standpoint, the drug finds its major usage as a premedicant or adjuvant (administered in the peri-induction period) to minimize the possibility of recall of unpleasant events during anesthesia and surgery. This is especially germane in patients who are unable to tolerate a sufficient depth of anesthesia to provide this amnesic effect on the basis of anesthetic agent alone. Quite often these patients are critically ill, and from a physiologic standpoint, their cardiovascular systems are unable to tolerate or adapt to moderate to deep anesthetic concentrations of the inhalation anesthetic agents. Even though the metabolic products of lorazepam are not active, the duration of action of this drug dictates that it not be used in the outpatient setting. Indeed, the drug probably should not be used in patients whose expected hospital stay is less than 72 hours. It appears that thrombosis or phlebitis after intravenous injection of lorazepam is less than with diazepam, especially if the drug is injected in small hand or arm veins. Most side effects of lorazepam are associated with central nervous system depression, are dose-related, and fairly predictable. Adverse central nervous system effects may be reversed by administration of physostigmine, but it is worthwhile to note that the duration of action of physostigmine, and repeated administration of physostigmine may be necessary. Lorazepam appears to be acceptable to both physicians and patients. There do not appear to be any obvious adverse interactions between lorazepam and other medications commonly used in anesthesia practice. Nevertheless, it appears that the major value of lorazepam to the anesthesiologist's armamentarium is its ability to prevent recall in appropriate situations.
 ...
PMID:Clinical pharmacology of lorazepam. 613 91

The pharmacokinetics and their relation to the pharmacodynamic properties of midazolam, the first water-soluble benzodiazepine derivative, are reviewed. Pharmacokinetically, midazolam is a unique derivative among the benzodiazepines. After both oral and parenteral routes of administration, it has a fast absorption rate, and differing from older derivatives it is very rapidly excreted with a half-life of only about 2 h. A reasonably good correlation has been found with the plasma levels and clinical effects, indicating a fast but short clinical response. Midazolam appears to be a useful short-acting hypnotic having almost no residual effects the following morning. In anesthesiology both oral and parenteral drug forms can be used for premedication. In addition, it is a new alternative for inducing anesthesia when a slow induction time is chosen or its advantageous properties: good cardiovascular stability, transient and mild respiratory depression, low frequency of venous irritation, production of anterograde amnesia, and short duration of action (last-mentioned property in comparison with other benzodiazepines).
 ...
PMID:Pharmacokinetics and the sedative effect of midazolam. 613 14


1 2 3 Next >>