Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “ANALEPTICS”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 631 records · Page 35Linked to original sources
PubMed1993

The effects of SCH 23390 and raclopride on cocaine-induced analepsis and EEG arousal in rabbits.

The effects of the dopamine D1 and D2 receptor antagonists on cocaine-induced, cholinergically-mediated analeptic and hippocampal theta activity in anesthetized rabbits were investigated. Cocaine (2 mg/kg, i.v.) reduced by 35% the duration of loss of righting reflex produced by a 25 mg/kg dose of pentobarbital. This shortening of narcosis time was blocked by pretreating the animals with the D1 antagonist, SCH 23390 (0.1 mg/kg) but not with the D2 antagonist raclopride (1-2 mg/kg). Cocaine (5 mg/kg, i.v.) also produced a short burst of increased hippocampal theta activity in urethane-anesthetized rabbits, which was also blocked by SCH 23390 but not by raclopride. An unexpected finding was that raclopride itself, at 2 mg/kg (i.v.), produced a marked activation of theta activity that lasted for 15-20 min. When cocaine was administered after this time it produced a potentiated theta response, both in duration and in magnitude. These results suggest that in the rabbit, cocaine exerts a cholinergically-mediated behavioral and EEG arousal through a D1 dopamine mechanism. The role of the D2 system is less clear but appears to be antagonistic to the D1-mediated response.

Analysis of Variance↗
PubMedDate not supplied

Delta9-tetrahydrocannabinol and pentobarbital as discriminative cues in the Mongolian Gerbil (Meriones unguiculatus)

Male Mongolian gerbils were trained to escape electric shocks in a T-shaped maze contingent upon the presence or absence of certain drug effects (state-dependency; StD). The drug discriminative cues used were those of either delta9-tetrahydrocannabinol (THC) or pentobarbital (P-barb.) vis-à-vis the respective vehicles. Several doses of THC (0.5-16.0 mg/kg) were used and compared with P-barb. (20.0 mg/kg), a dose at which the most rapid drug discrimination occurs in the rat. When drug discrimination was established dose-time- and transfer characteristics for the training drugs were studied. Possible potentiation and antagonism was also examined in the pentobarbital trained gerbils. It was found that none of the THC doses were discriminated as rapidly as that of P-barb. Decreasing the amounts of training drug administered or increasing the injection-test intervals resulted in a decline of the number of drug associated choices. There was a maximum of 40% drug choices between THC and P-barb at the transfer tests. Mixtures of the two compounds increased the number of drug choices in an additive or even more than additive manner. Amphetamine (4.0 mg/kg) did not interact with the P-barb. induced choice responding. The analeptic drug, bemegride was found effective in antagonizing the P-barb. cued choice behavior.

Amphetamine↗
PubMed1983

Interaction of the discriminative stimulus properties of diazepam and ethanol in pigeons.

One group of pigeons (n = 5) was trained to discriminate between the effects induced by 5.6 mg/kg of diazepam (DZP) and the vehicle whereas other pigeons (n = 5) had to discriminate between 3.0 g/kg of ethanol (ETOH) and the vehicle, administered intragastrically (IG) 10 and 40 min prior to the training sessions respectively. Once trained, the pigeons were tested with either diazepam or ethanol alone and in combination. The birds trained to discriminate between DZP and the vehicle mostly performed non-drug associated responses when tested with ETOH (0.56 to 3.0 g/kg). Tests with other doses of DZP (0.3 to 3.0 mg/kg) in the diazepam-trained birds resulted in an ED50 value of 1.4 mg/kg. The birds trained to discriminate between ETOH and the vehicle generalized DZP to ETOH, the ED50 value for diazepam being 3.0 mg/kg. Tests with other doses of ETOH (0.56 to 2.0 g/kg) in this latter group resulted in an ED50 value of 1.3 g/kg. Tests with combinations of DZP and ETOH produced a shift of the dose-response curves to the left indicating drug additivity. The discrimination of 5.6 mg/kg of IG administered DZP but not that of ETOH (3.0 g/kg) was attenuated by injections of the analeptic bemegride (ED50 = 5.5 mg/kg), thus suggesting a difference in the cueing processes of the two drugs. When tested singly, bemegride induced non-drug responding or complete suppression of responding in the birds at the doses of 3.0 and 10.0 mg/kg respectively. In conclusion, the discriminable effects of DZP and ETOH are additive or even supra-additive, but the stimulus properties of the two drugs are not identical.

Animals↗
PubMed1987

Differential convulsive susceptibility of high-activity and low-activity selected mice in response to GABA antagonists.

Lines of mice selectively-bred for High and Low-Activity in an open-field maze were tested for seizure susceptibility to three analeptics: flurothyl, pentylenetetrazol and bicuculline. The major finding was that two replicate High-Activity lines were more susceptible to myoclonic convulsions but less susceptible to clonic convulsions than their respective replicate Low-Activity lines. The major exception to this finding was that the High and Low-Activity lines did not differ for bicuculline-induced clonus although females tended to conform to the general pattern. These results are interesting because they demonstrate that diametrically opposite susceptibility to myoclonus and clonus is not an isolated phenomenon. Similar seizure susceptibility patterns and activity differences have also been reported for the Long-Sleep and Short-Sleep selectively-bred mouse lines. Further, since the progenitor population of the High-Activity and Low-Activity lines were developed from strains that were also part of the progenitor population of the Long-Sleep and Short-Sleep lines, it is hypothesized that some of the same alleles underwent selection in both selective-breeding programs.

Animals↗
PubMed1990

Effects of two benzodiazepine inverse agonists, RO 15-4513 and FG 7142, on recovery from pentobarbital and halothane anesthesia in the rat.

A new class of drugs, the benzodiazepine inverse agonists, have recently been shown to antagonize some of the behavioral and sedative effects of benzodiazepines, barbiturates, and alcohol. Preliminary studies suggested that at least one of these drugs, RO 15-4513, may also be able to reverse the general anesthetic properties of volatile halogenated agents. Another inverse agonist, FG 7142, exhibits a similar ability to antagonize alcohol or benzodiazepines. However, FG 7142 is less potent than RO 15-4513 and has less affinity for the benzodiazepine receptor (BZR). The present studies were therefore undertaken to compare the analeptic effects and relative potencies of RO 15-4513 and FG 7142 on the anesthetic properties of pentobarbital compared with the general anesthetic agent halothane as measured by the time for recovery of the righting reflex in the rat. Three basic experimental paradigms were employed. Drug (FG or RO) or carrier was administered 5 minutes prior to the induction of pentobarbital anesthesia. Drug or carrier was administered to anesthetized animals 60 minutes after pentobarbital injection. Lastly, drug or carrier was administered 5 minutes prior to 15 minutes of halothane anesthesia. In addition, the selective benzodiazepine antagonist, flumazenil (RO 15-1788), was used to determine if the effects of the benzodiazepine inverse agonists on recovery from barbiturate or halothane anesthesia were due to activity at the BZR. The results revealed that RO was both more potent and more effective than FG at speeding recovery from barbiturate anesthesia in the rat. RO's effects appeared to be primarily due to BZR inverse agonist activity since it could be reversed by the BZR antagonist, flumazenil.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia Recovery Period↗
PubMed1991

Central ventilatory effects of thyrotropin-releasing hormone in the conscious rat.

Thyrotropin-releasing hormone was shown to exert potent ventilatory effects after central administration. These data, however, were derived from studies using anesthetized animal preparations. Since TRH elicits strong arousal reactions, the observed ventilatory effects of TRH under anesthesia may have been due to nonspecific reduction in the anesthetic state of the animals. In order to clarify the extent to which the reversal of anesthesia may change ventilatory parameters after TRH application, we investigated the effect of TRH on ventilation rate, relative tidal volume, relative respiratory minute volume, CO2 production CO2 consumption, and locomotor activity in the conscious, unrestrained rat. Intracerebroventricular application of TRH induced a dose-dependent, sustained increase in ventilation rate, relative tidal volume, and relative respiratory minute volume of maximally 128%, 890%, and 235%, respectively. In addition, CO2 production and O2 consumption were elevated by 4.6 and 11.7 fold, while no significant changes in locomotor activity were observed. The results suggest that TRH stimulates ventilation by a mechanism independent of its analeptic properties.

Animals↗
PubMed1993

The effect of TRH on ethanol-induced sedation in alcohol-preferring and -nonpreferring rats.

TRH antagonism of ethanol sedation was evaluated in selectively-bred alcohol-preferring (P) and -nonpreferring (NP) rats. Intracerebroventricular (i.c.v.) infusions of TRH significantly reduced sleep time in the NP rats. In the P rats, TRH tended to reduce sleep, but this reduction was not significant. TRH had no significant effect on peripheral blood alcohol concentrations. The present results show that NP rats are more sensitive to the analeptic effect of TRH compared to P rats. These data support and extend those of others who have demonstrated a TRH antagonism on drug-induced sedation. Differential sensitivity to TRH may reflect differences in TRH receptor activity and/or TRH metabolism. Sensitivity to TRH analepsis may be associated with sensitivity to ethanol.

Animals↗
PubMed1982

Neuropharmacological evaluation of RX 77368--a stabilised analogue of thyrotropin-releasing hormone (TRH).

L-Pyroglutamyl-L-histidyl-L-2,3-dimethylprolineamide (Pyr-His-Dmp . NH2; RX 77368) a stabilised analogue of thyrotropin-releasing hormone (TRH) has been examined for neuropharmacological effects in animal tests. The compound was more potent than either TRH or clinically established drugs in four animal tests of antidepressant potential (reserpine reversal, clonidine antagonism, tremorine reversal and learned immobility). RX 77368 also antagonised barbiturate sleeping time. Given by itself to rats the peptide produced arousal as characterised by EEG and EMG measurements and delayed the onset of sleep. The arousal induced was not accompanied by increases in locomotor activity. The profile of pharmacological activity for RX 77368 did not correspond to the profiles of tricyclic antidepressants, psychic-stimulants or analeptic drugs. The possible clinical uses for such a molecule are discussed.

Adult↗
PubMed1989

Respiratory and cardiovascular effects of thyrotropin-releasing hormone as modified by isoflurane, enflurane, pentobarbital and ketamine.

Thyrotropin-releasing hormone (TRH) possesses significant arousing and cardio-respiratory stimulant actions. The effects of a 2 mg/kg i.v. bolus dose of TRH on respiration and systemic hemodynamics were compared in conscious, freely-moving rats and during anesthesia with 4 different anesthetics. Fifty-four male Sprague-Dawley rats weighing 285 +/- 4 g (mean +/- S.E.M.) were divided into 5 groups: conscious, enflurane (2%), isoflurane (1.4%), pentobarbital (8 mg/kg/h i.v.), and ketamine (60 mg/kg/h i.v.). Anesthetized rats were intubated and breathed oxygen or anesthetic/oxygen spontaneously. Aortic blood pressure, heart rate, cardiac output, respiratory rate, arterial blood pH, blood gases, lactate and glucose were measured, and data were collected over a 20 min baseline period and for 130 min post-TRH. TRH increased respiratory rate in all groups; concomitant changes in arterial PCO2 indicated increased minute ventilation in the inhalation agent groups but not in the i.v. anesthetic groups or in the awake group. Significant respiratory depression in the enflurane group was rapidly reversed by TRH. The respiratory stimulant and arousing effects of TRH were smallest with ketamine anesthesia. The hemodynamic responses to TRH were consistent with a pattern of sympathoadrenalmedullary activation and were relatively uniform across groups despite anesthetic-induced alterations in baseline values. TRH or its analogues may prove useful as an analeptic in clinical anesthesia.

Animals↗
PubMed1990

The search for the hypnogenic center.

1. Electrophysiological and lesion studies have suggested that a number of specific sites in the brainstem and basal forebrain may be involved in the regulation of sleep and waking. In contrast, a study of glucose consumption as measured by the 2-deoxyglucose technique reported a generalized decrease in nonREM sleep compared to waking. The rate of protein synthesis was relatively unchanged in nonREM sleep. 2. Another approach to understanding sleep regulation is to study the mechanism by which hypnotic drugs affect the nervous system. This may be done at both a molecular and neuroanatomic level. Studies with B-carbolines, inverse agonists of benzodiazepines (BZs), indicate that sleep induction by BZs is mediated by binding at the BZ recognition site of the BZ receptor complex. Binding at this site by a long-acting B-carboline parallels the time course of its arousing effects. A study with an enantiomeric BZ indicates that the effects on sleep are stereospecific. It is conceivable that some inverse agonists or enantiomeric benzodiazepines might be developed for clinical use as analeptics. 3. Microinjection of a BZ into the dorsal raphe nucleus acutely increases wakefulness, while administration into the medial preoptic area of the hypothalamus enhances sleep maintenance.

Animals↗
PubMedDate not supplied

Computer-determined EEG patterns associated with memory-facilitating drugs and with ECS.

Cortical EEG patterns of rats were analyzed by computer following administration of analeptic drugs at doses previously shown to facilitate posttrial memory processes. The drugs produced an increase in the power of the EEG primarily by increasing the amount of activity in delta and lower-theta frequency bands. The increase in lower frequency theta was accompanied by a decrease in higher frequency theta, thus increasing the regularity in the theta band. Electroconvulsive shock, which disrupts posttrial memory processes, also increased delta activity, but it greatly lowered amplitudes throughout the EEG frequency spectrum. It is concluded that if any consistent relationship between the cortical EEG and posttrial memory processes exists, then increased amplitude and regularity in the delta and theta bands are associated with increased amounts of memory storage--at least in alert animals. Further studies are required to determine if a causal influence is involved in this correlation.

Animals↗
PubMed1988

Ethanol and Ro 15-4513: behaviour maintained by operant procedures (DRL-72s and PTZ-drug discrimination) in rats.

The proposed amethystic imidazobenzodiazepine Ro 15-4513 and ethanol (ETOH) were examined in rats using two operant procedures, differential reinforcement of low rates of responding (DRL), and drug discrimination learning (DDL). In the first bar-pressing responses occurring 72 s or longer after the last reinforcement were rewarded; responses occurring earlier reset the time schedule. In the latter, animals were trained to discriminate between the effects of the analeptic pentylenetetrazole (PTZ) and the non-drug condition; the schedule of reinforcement was FR-10. Water was the reinforcer. A dose of 1000 mg/kg ETOH decreased the rate of bar pressing in the DRL experiment; doses of 300 and 560 mg/kg ETOH did not. The decrease was not attenuated by Ro 15-4513. No significant deviations from baseline responding occurred with Ro 15-4513 (1, 3 10 mg/kg). The number of reinforcements increased significantly after ETOH (1000 mg/kg), but not after Ro 15-4513. Combinations of the two agents produced increases in the number of reinforcements. Changes in DRL behaviour induced by diazepam (1 and 10 mg/kg) were normalized by 3 mg/kg Ro 15-4513. In DDL, Ro 15-4513 (10 mg/kg) substituted for PTZ; ETOH did not. Diazepam and Ro 15-1788 attenuated the response generalization from Ro 15-4513 to PTZ; ETOH did not. There was a dose-related increase in the time to complete the DDL tests after ETOH treatment; addition of Ro 15-4513 increased the time further. In conclusion, antagonism between Ro 15-4513 and ETOH did not occur in the present studies; data are furthermore consistent with the view that Ro 15-4513 acts as a partial inverse benzodiazepine agonist.

Animals↗
PubMed1995

The ethnopharmacology of Madeira and Porto Santo Islands, a review.

The ethnopharmacology of Madeira and Porto Santo Islands is extremely interesting because of the cultural and biogeographic features of this region, which make it a centre of medicinal plant diversity (richness of endemic flora, geographical isolation in the Atlantic sea, crosscultural influences, and past abundance of local healers). The medicinal flora of Madeira is composed of 259 species. Some noteworthy medicinal taxa, endemic or locally relevant, are: Acanthus mollis, Aeonium glandulosum, Aeonium glutinosum, Bidens pilosa, Borago officinalis, Chamaemelum nobile var. discoideum, Culcita macrocarpa, Echium nervosum, Euphorbia platiphylla, Helichrysum melaleucum, Helichrysum obconicum, Hypericum glandulosum, Hypericum humifussum, Kleinia repens, Laurus azorica, Monizia edulis, Ocotea foetens, Psoralea bituminosa, Rubus bollei, Rumex maderensis, Sambucus lanceolata, Scilla maderensis, Sedum brissemoretii, Sedum farinosum, Sedum nudum, Sibthorpia peregrina, Teucrium betonicum, Thymus caespititius, Trifolium squamosum and Vaccinium padifolium. Among the medicinal cryptogams, one can underline the parasitic fungus Laurobasidium lauri, which grows on the stems of Laurus azorica and is used as an antirheumatic, haemostatic, emmenagogue, insecticide and analeptic.

Medicine, Traditional↗
PubMedDate not supplied

Theophylline-induced changes in the mouse brainstem auditory evoked potential.

Because theophylline is a widely used analeptic, there is interest in its possible ototoxic and neurotoxic effects. The present study used the brainstem auditory evoked potential (BAEP) to evaluate the acute effects of theophylline on auditory electrophysiology in mice. Adult female C57BL/6 mice were injected intraperitoneally with 150 mg/kg theophylline or saline. The BAEP thresholds and latency-intensity profiles suggested that theophylline induced a rather slight but statistically significant change in auditory function that was suggestive of a temporary recruitment-type sensorineural deficit. This observation raises concerns about the possible ototoxic effects of theophylline, particularly in asthmatic patients and apneic preterm neonates who receive this drug chronically. While there was BAEP evidence of ototoxic effects for theophylline, there was no evidence of neurotoxic effects.

Animals↗
PubMed1998

Spectrum of gestational exposure to illicit drugs and other xenobiotic agents in newborn infants by meconium analysis.

OBJECTIVE: To detect the spectrum of gestational exposure to illicit drugs and other xenobiotic agents in neonates by meconium analysis. METHOD: Meconium was collected from 98 neonates and analyzed for illicit drugs and other xenobiotic agents by high-performance liquid chromatography and gas chromatography/mass spectrometry. RESULTS: Eighty-one (82.7%) infants tested positive for xenobiotic agents, and each infant had from 1 to 9 drugs present. These included local anesthetics (30%) such as lidocaine and mepivacaine; food additives (25%) such as ionol (butylated hydroxytoluene); illicit drugs (11%), especially cocaine and morphine; analgesics (10%) such as meperidine; and fewer (< 10%) other drugs such as antihistamines, antidepressants, adrenergics, anticonvulsants, cough medications, analeptics, hypnosedatives, and cardiotonics. CONCLUSION: We demonstrated substantial exposure of neonates to xenobiotic agents, ranging from exposure to food additives, prescribed or over-the-counter medications, and drugs of abuse.

Chromatography, High Pressure Liquid↗
PubMed1998

An update on the CNS actions of TRH and its analogs.

This brief review will discuss the recent literature on several of the central actions of TRH and its analogs. The most prominent of these actions include: (1) the arousal or analeptic effect in drug narcotized animals or in concussion models; (2) the reversal of cognitive deficits produced by various drugs or procedures, and (3) the improvement of several neurological deficits produced in animal models of spinal and/or cerebellar injury. The mediation of these TRH effects by neurotransmitters is discussed. While little has been published on the human neuropsychopharmacology of TRH, and especially of its analogs, the future holds considerable therapeutic promise for these interesting drugs.

Animals↗
PubMed2002

Cocaine regulates TRH-related peptides in rat brain.

Cocaine administration has previously been reported to alter the levels of prepro-TRH mRNA and TRH (pGlu-His-Pro-NH(2)) in the limbic system of rats (J. Neurochem. 60 (1993) 1151). We have now demonstrated that a previously unrecognized family of TRH-like peptides is involved in the actions of cocaine. We treated young adult male Sprague-Dawley rats (five per group, 250g body weight at sacrifice) for 2 weeks with either twice daily injections of saline (control group), twice daily injections of 15mg/kg cocaine until sacrifice (chronic group), single injection of 15mg/kg cocaine 2h prior to sacrifice (acute group) or chronic cocaine injections replaced by saline injections 72h prior to sacrifice (withdrawal group (WD)). Twelve different brain regions were dissected and immunoreactivity for TRH (TRH-IR), EEP (pGlu-Glu-Pro-NH(2); EEP-IR) and related peptides were measured by radioimmunoassay (RIA). High pressure liquid chromatography (HPLC) revealed that in many brain regions EEP-IR and TRH-IR consisted of a mixture of TRH, and other TRH-like peptides including EEP, pGlu-Val-Pro-NH(2) (Val(2)-TRH), pGlu-Tyr-Pro-NH(2) (Tyr(2)-TRH), pGlu-Leu-Pro-NH(2) (Leu(2)-TRH), and pGlu-Phe-Pro-NH(2) (Phe(2)-TRH). Following i.p. injection, these TRH-like peptides readily crossed the blood-brain barrier but cleared very slowly from brain tissues. Acute cocaine produced a 4.1-fold increase in Val(2)-TRH level in medulla while Val(2)-TRH and Tyr(2)-TRH, increased 6.2- and 2.9-fold, respectively in pyriform cortex PYR. TRH and Leu(2)-TRH, decreased 47 and 93%, respectively in the nucleus accumbens (AM) while other EEP-IR peaks decreased 50-100% consistent with the significant decrease in total EEP-IR in the AMs following acute cocaine treatment. Because 2h is too short a time to alter levels of neuropeptides via changes in the rate of biosynthesis, the acute cocaine-induced elevation or reduction in TRH and related peptides is most likely due to suppression or stimulation, respectively, of the corresponding peptide secretion rate. Because TRH and TRH-like peptides have antidepressant, analeptic and euphorigenic properties, we conclude that these endogenous substances are potential mediators of both the cocaine "high" and withdrawal symptoms.

Animals↗
PubMed2002

Design, synthesis, and biological evaluation of novel, centrally-acting thyrotropin-releasing hormone analogues.

Novel, metabolically stable and centrally acting TRH analogues with substituted pyridinium moieties replacing the [His(2)] residue of the endogenous peptide were prepared by solid-phase Zincke reaction. The 1,4-dihydropyridine prodrugs of these analogues obtained after reducing the pyridinium moiety were able to reach the brain and maintain a sustained concentration of the charged, degradation-resistant analogues formed after enzymatic oxidation of the prodrug, as manifested by the analeptic action measured in mice. Among the four analogues reported, compound 2a showed the highest potency and longest duration of action in reducing the pentobarbital-induced sleeping time compared to the parent TRH. No binding to the endocrine TRH-receptor was measured for 2a; thus, this compound emerged as a potent, centrally acting TRH analogue.

Animals↗