Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “LYSERGIC ACID DIETHYLAMIDE”

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 1,243 records · Page 69Linked to original sources
PubMed2005

Prognostic impact of psychoactive substances use during hospitalization for intentional drug overdose.

OBJECTIVE: To assess whether current use of psychoactive substance(s) is a prognostic factor during hospitalization for intentional drug overdose (IDO). METHOD: Current intoxication with psychoactive substance(s) [cannabis, opiate, buprenorphine, amphetamine/ecstasy, cocaine, lysergic acid diethylamide (LSD)] was identified using toxicological urinalysis in 671 patients with IDO. An IDO was a priori defined as serious if associated with one of the following events: death, hospitalization in intensive care unit longer than 48 h, respiratory support, use of vasopressive drugs, cardiac massage or dialysis. RESULTS: Subjects positive for toxicological assays were twice as likely to present with serious IDO (OR = 1.9, 95% CI: 1.3-2.8, P = 0.001), independently from a large range of confounding factors. The risk of serious IDO was especially marked in subjects using LSD, buprenorphine or opiates. CONCLUSION: Systematic investigation of substance use could be important to adapt medical management of subjects with IDO in general hospital, but also in primary care and psychiatric settings.

Adult↗
PubMed1992

The canine internal carotid system: regional differences in reactivity to nerve stimulation, noradrenaline and 5-hydroxytryptamine.

Reactivity of the canine internal carotid system to field electrical stimulation, noradrenaline and 5-hydroxytryptamine was determined isometrically using 4-mm cylindrical rings from the cervical and cavernous portions and middle cerebral artery. Electrical stimulation at supramaximal voltage (0.5-4 Hz, 0.2 ms duration) produced a frequency-dependent contraction that was similar in cervical and cavernous portions and lower in the middle cerebral artery. This response was blocked by tetrodotoxin (10(-6) M) or phentolamine (10(-6) M). Noradrenaline (10(-9) - 3 x 10(-4) M) produced concentration-dependent contractions and the sensitivity was: cervical portion = cavernous portion greater than middle cerebral artery, and this effect was blocked by phentolamine (10(-6) M). 5-hydroxytryptamine (10(-9) - 10(-5) M) caused concentration-dependent contractions and the sensitivity was: cervical portion less than cavernous portion less than middle cerebral artery. This response was depressed by lysergic acid diethylamide (10(-6) M). The results indicate that reactivity of the internal carotid system: (a) to alpha adrenergic activation by endogenous and exogenous noradrenaline is lower in the distal segment (middle cerebral artery) than in the proximal segments (cervical and cavernous internal carotid artery) and (b) to tryptaminergic activation increases as it courses toward the brain. Therefore, functional characteristics could be related to embryological origin which the segments of this vascular system are derived from.

Animals↗
PubMed1993

Effects of dopamine on the gastrointestinal tract of chicks.

The effects of dopamine on the gastrointestinal tract of chicks have been investigated. Dopamine caused concentration-related contractions of the upper oesophagus, crop or lower oesophagus but relaxed the duodenum, ileum, large intestine or caecum in a concentration-related fashion. By means of specific antagonists, the presence of muscarinic, histamine (H1), alpha-adrenergic, 5-HT-ergic and dopaminergic receptors were established in the lower oesophagus and their stimulation caused contraction while beta-adrenergic-receptor stimulation caused relaxation. Contraction of the lower oesophagus induced by dopamine was abolished by lysergic acid diethylamide and was antagonized by moderate concentrations of haloperidol or pimozide. Tachyphylaxis developed to repeated administration of a large concentration of dopamine. These findings suggest that contraction of the lower oesophagus of chicks by dopamine is largely mediated by 5-hydroxytryptamine release and that stimulation of dopaminergic receptors contributes to a lesser extent.

Acetylcholine↗
PubMed1982

5-Hydroxytryptamine receptors of visceral primary afferent neurones on rabbit nodose ganglia.

1. The electrophysiological characteristics of 5-hydroxytryptamine (5-HT) receptors distributed on visceral primary afferent neurones (the nodose ganglion cells of the vagus) in rabbits were investigated with intracellular recording and voltage-clamp techniques.2. In response to 5-HT applied by superfusion (>/= 10 mum) or by ionophoresis (>/= 5 nA, 50 msec), the majority of type C neurones (mean axonal conduction velocity: 0.83+/-0.25 m/sec) showed a rapid depolarization of 20-30 mV in amplitude which was followed by a hyperpolarization of a few millivolts. Both the initial depolarization and afterhyperpolarization were associated with a reduction in membrane resistance.3. Type A neurones (mean axonal conduction velocity: 7.7+/-0.4 m/sec) did not show any significant alterations in membrane potential and resistance during or after application of 5-HT.4. The initial depolarization induced by 5-HT was abolished by Na(+)-free Krebs solution and showed a reduction of a few millivolts in K(+)-free or Ca(2+)-free Krebs solution. The response in normal Krebs solution was reversed at a membrane potential level of +7.3+/-1.1 mV.5. The afterhyperpolarization disappeared in Na(+)-free or Ca(2+)-free Krebs solution, while it was markedly enhanced in K(+)-free Krebs solution. The response in normal Krebs solution reversed at a membrane potential of -88.7+/-0.8 mV, and was abolished at membrane potentials more positive than -20 mV.6. Unlike 5-HT voltage responses, which were biphasic in the majority of neurones examined, 5-HT induced currents were usually monophasic when recorded at holding membrane levels ranging from -80 to +50 mV. The reversal potential of the inward current was +7.5+/-0.8 mV which was in good agreement with the reversal level for 5-HT-induced depolarizations. The reversal potentials for inward currents which were obtained at various concentrations of Na(+) or K(+) corresponded to the theoretical values calculated by the equivalent circuit equation.7. These results suggest that the initial depolarization induced by 5-HT is due mainly to simultaneous increases in Na(+) and K(+) conductances, while the afterhyperpolarization is brought about by an increase of K(+) conductance which is triggered by a voltage-dependent influx of Na(+) and Ca(2+).8. The mean value for the ;limiting slope' of conductance change vs. 5-HT concentration and the slope of 5-HT current vs. 5-HT concentration obtained by superfusion of 5-HT, were in good agreement, 1.84+/-0.26 and 1.88+/-0.31, respectively. On the other hand, the mean Hill coefficient obtained from the dose-response curves for the inward current induced by ionophoresis was 2.51+/-0.14.9. Tetrodotoxin (0.2 mum) blocked the soma action potential completely, but did not show any effect on 5-HT-induced responses.10. (+)-Lysergic acid diethylamide and methysergide (1-100 mum) had no depressant effect on the 5-HT-induced depolarization.11. (+)-Tubocurarine at low concentrations (1-5 mum) inhibited the 5-HT induced inward current competitively. The mode of its inhibitory action became noncompetitive at higher concentrations (10-20 mum).

Animals↗
PubMed2002

Differential activation of Gq/11 and Gi(3) proteins at 5-hydroxytryptamine(2C) receptors revealed by antibody capture assays: influence of receptor reserve and relationship to agonist-directed trafficking.

As determined by a guanosine 5'-O-(3-[(35)S]thio)triphosphate ([(35)S]GTPgammaS) binding assay, which does not distinguish G protein subtypes, 5-hydroxytryptamine (5-HT) and 2(S)- 1-(6-chloro-5-fluoro-1H-indol-1-yl)-2-propanamine fumarate (Ro600175) behaved as full agonists at human 5-HT(2C) (h5-HT(2C)) receptors (VSV isoform) stably expressed in Chinese hamster ovary (CHO) cells, whereas 1-2,5-dimethoxy-4-iodophenyl-2-aminopropane (DOI), d-lysergic acid diethylamide (LSD), and lisuride exhibited partial agonist properties. After treatment with pertussis toxin to uncouple 5-HT(2C) receptors from Gi/Go but not Gq/11, DOI and LSD were as efficacious as 5-HT and Ro600175 in stimulating [(35)S]GTPgammaS binding, whereas lisuride still exhibited low efficacy (40%). Correspondingly, in a scintillation proximity assay employing specific antibodies against Gq/11, 5-HT, Ro600175, DOI, and LSD behaved as high-efficacy agonists, whereas lisuride showed efficacy of 36%. In contrast, when employing a specific antibody recognizing Gi(3), DOI and LSD were less efficacious (80 and 30%, respectively) than 5-HT and Ro600175, and lisuride was inactive. Agonist actions were specifically mediated by h5-HT(2C) receptors inasmuch as the selective 5-HT(2C) antagonist SB242,084 blocked [(35)S]GTPgammaS binding at both Gq/11 and Gi(3). Agonist potency for stimulation of Gi(3) was ~6- to 8-fold less than for Gq/11, indicating that the latter was preferentially engaged by h5-HT(2C) receptors. Inactivation of h5-HT(2C) receptors with the alkylating agent N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline did not modify the efficacy of 5-HT, Ro600175, and DOI at Gq/11, whereas their efficacies were substantially reduced at Gi(3), indicating a greater receptor reserve for the former. Finally, the preferential activation of Gq/11 versus Gi(3) by DOI, LSD, and lisuride was diminished in the presence of lower receptor number. In conclusion, h5-HT(2C) receptors couple to both Gq/11 and Gi(3) in CHO cells, and efficacy for G protein subtype activation is both ligand- and receptor reserve-dependent.

Alkylation↗
PubMed1979

Chemotherapy of parasitic worms: new biochemical strategies.

Many chemotherapeutic agents that are effective against parasitic helminths affect cellular regulatory sites that control motility, metabolism, chemotaxis, and egg formation. Serotonin receptors are present in several species of parasitic flatworms and appear to participate in the regulation of motility and carbohydrate metabolism. In Fasciola hepatica these receptors are coupled to an adenylate cyclase through a cellular component that requires guanosine triphosphate. Serotonin is the most potent indoleamine agonist, while lysergic acid diethylamide and its 2-bromo derivative are the most potent antagonists. These studies are revealing additional sites in trematodes that may be important for the development of new and more selective chemotherapeutic agents.

Adenylyl Cyclases↗
PubMed2000

Muscle changes in the neuroleptic malignant syndrome.

AIMS: To characterise the skeletal muscle changes in the neuroleptic malignant syndrome (NMS). METHODS: Detailed light and ultrastructural examination was carried out on skeletal muscle from three cases of NMS, two associated with recreational drugs (3,4-methlenedioxymethylamphetamine (MDMA, Ecstasy) and lysergic acid diethylamide (LSD)) and one with antipsychotic drugs (fluoxetine (Prozac) and remoxipride hydrochloride monohydrate (Roxiam)). RESULTS: The muscles were grossly swollen and oedematous in all cases, in one with such severe local involvement that the diagnosis of sarcoma was considered. On microscopy, there was conspicuous oedema. In some fascicles less than 10% of fibres were affected whereas in others more than 50% were pale and enlarged. There was a spectrum of changes: tiny to large vacuoles replaced most of the sarcoplasm and were associated with necrosis. A striking feature in some fibres was the presence of contraction bands separating segments of oedematous myofibrils. Severe endomysial oedema was also detectable. There was a scanty mononuclear infiltrate but no evidence of regeneration. CONCLUSIONS: The muscle changes associated with NMS are characteristic and may be helpful in differential diagnosis.

Adult↗
PubMed1993

Expression of 5-HT1C receptors in transfected MDCK cells is functionally and anatomically asymmetric.

Madin-Darby canine kidney (MDCK) cells were transfected with the cDNA for the rat 5-HT1C receptor (pMV7-SR1c) using electroporation. Cells that survived G418 selection medium were loaded with indo-1 and run through a fluorescence-activated cell sorter (FACS); 10% responded to serotonin (5-HT) with an increase in intracellular Ca2+ concentration ([Ca2+]i). Responding cells were separated with the FACS, grown to confluence, and resorted two more times until a clone of 100% respondents was obtained (SR-MDCK). In SR-MDCK cells grown on porous filters, [Ca2+]i increased only when 5-HT was applied to the basolateral membrane (change in [Ca2+]i = 190 +/- 43 nM); there was no response of [Ca2+]i to apical application of 5-HT. The asymmetric response to 5-HT was likely due to targeting of 5-HT1C receptors exclusively to the basolateral membrane of SR-MDCK cells; 125I-labeled lysergic acid diethylamide binding sites, a marker of high-affinity 5-HT receptors, were located only in the basolateral membrane. These experiments demonstrate that epithelial cells can be stably transfected to express G protein-linked, calcium-mobilizing receptors and that the receptors may be targeted asymmetrically to specific domains of the plasma membrane.

Animals↗
PubMedDate not supplied

Differential binding of ergot compounds to human versus rat 5-HT2 cortical receptors.

Eleven ergot compounds were competed against [3H]-ketanserin-labelled 5-HT2 receptors in rat and human cortex. Four of the ergots are selective for rat 5-HT2 receptors--mesulergine, methysergide, nicergoline and metergoline, whereas pergolide, d-lysergic acid, ergonovine, ergotamine, d-lysergic acid diethylamide, lisuride and dihydroergotamine display selectivity for human 5-HT2 receptors. Rat-selective compounds contain a methyl substitution on the indole nitrogen, whereas human-selective compounds contain a hydrogen. This structural feature may allow the two groups of ergots to differentiate between the two species of receptors.

Animals↗
PubMed1982

Enhancement by progesterone of 5-hydroxytryptophan inhibition of the copulatory response in the female rat.

A study was made of the influence of different hormonal treatments used to induce copulatory behavior in ovariectomized female rats (lordosis behavior), on the effects of an endogenous increase of 5-HT or catecholamines achieved by DL-5-HTP and L-Dopa. The lordosis response (LR) has been shown to be inhibited by increased serotonergic and catecholaminergic neuronal activity. The 5-HT agonist lysergic acid diethylamide (LSD) has been found to inhibit the LR. This effect was recently shown to be enhanced by increasing doses of progesterone. In the present study it was demonstrated that the inhibitory effect of the 5-HT precursor 5-hydroxytryptophan was also potentiated by increased doses of progesterone. However, the effect of DL-5-HTP on spontaneous behaviors in an exploratory situation was not influenced by progesterone treatment. In contrast to the results with DL-5-HTP, progesterone had no modulating effects on the lordosis-inhibiting action of the catecholamine precursor levo-dopa. This elective effect on the influence of a progesterone-dependent response suggests a direct relationship between 5-HT mechanisms and the progesterone action involved in the LR. Possible mechanisms underlying the observed interactive effect of progesterone and serotonin on lordosis behavior, such as a progesterone-induced alteration of serotonergic transmission, are discussed.

5-Hydroxytryptophan↗
PubMed1981

Receptors for 5-hydroxytryptamine in rabbit isolated ear artery and aorta.

The effects of N,N'-bis-(O-methoxybenzylaminohexyl)-cystamine tetrahydrochloride (BHC), 2-brom-d-lysergic acid diethylamide (BOL) and prazosin on 5-hydroxytryptamine (5-HT) dose-response curves in rabbit ear artery and thoracic aorta were determined. BHC, an irreversible alpha-adrenoceptor antagonist, and prazosin had no substantial effect while BOL shifted the 5-HT dose-response curve to the right in aorta. BHC shifted the curve to the right and reduced maximal response to 5-HT in ear artery. BOL shifted the curve to the right only above 10(-6) M 5-HT in control, but at all concentrations studied in BHC-pretreated ear arteries. In vitro denervation of the ear artery with 6-hydroxydopamine did not significantly alter the 5-HT dose-response curve, nor the effect of BHC on that curve. On the other hand, desipramine decreased the contractile response to high concentrations of 5-HT in non-denervated ear arteries. Prazosin increased the 5-HT threshold and slope of the curve in the ED50 region, but had no inhibitory effect on contractile responses above 3 x 10(-7) M 5-HT or on maximal response. It is concluded that 5-HT acts exclusively on 5-HT receptors in aorta, but on both alpha-adrenergic and 5-HT receptors in ear artery. 5-HT also possesses a small indirect sympathomimetic action at high concentrations in the ear artery. Prazosin has no effect on 5-HT receptors in either vessel and blocks the alpha-adrenoceptor stimulation by 5-HT in ear artery.

Animals↗
PubMed2004

The right of minors to confidentiality and informed consent.

Doctor-patient confidentiality is a precept of adolescent medicine. In general, physicians honor the privacy of adolescents unless there is evidence that the youngster is engaging in dangerous activities. An otherwise healthy 16 year old was referred for headache evaluation. During the portion of the interview conducted outside the presence of his mother, the patient revealed using marijuana and cocaine regularly and LSD (lysergic acid diethylamide), hallucinogenic mushrooms, and "Ecstasy" (3,4-methylenedioxymethamphetamine) occasionally. Given this information, and as allowed by North Carolina's General Statutes, the patient was offered confidential treatment for illegal substance abuse; he declined the offer. He also turned down the request to forgo his right to privacy so that his parents could be made aware of his addiction. As a result of the patient's drug use and disregard of its consequences, it was determined that notification of a parent was essential to his life or health; thus, confidentiality was breached. Although substance abuse is a behavior that threatens the abuser's health and life, state and federal laws vary regarding the rights of minors to confidential evaluation and treatment. For this article, laws that govern minors' rights to consent to confidential treatment for illegal substance abuse were reviewed. The aforementioned case is used as a catalyst for discussion.

Adolescent↗
PubMed1995

Hair analysis for drugs of abuse. X. Effect of physicochemical properties of drugs on the incorporation rates into hair.

To determine the mechanism involved, the incorporation rate (ICR) of drugs into hair was compared to melanin affinity, lipophilicity and membrane permeability. The following 20 drugs were tested; amphetamine, methamphetamine, p-hydroxyamphetamine, p-hydroxymethamphetamine, cocaine, benzoylecgonine, ecgonine methyl ester, morphine, 6-acetylmorphine, phencyclidine, 1-(1-phenyl)-piperidinyl-cyclohexanol, methylenedioxyamphetamine, methylenedioxymethamphetamine, methoxyphenamine, O-desmethyl methoxyphenamine, benzphetamine, norbenzphetamine, deprenyl, lysergic acid diethylamide (LSD) and 11-nortetrahydrocannabinol-9-carboxylic acid (THCA). Their ICRs were represented as the ratios of the drug concentrations in rat hair to AUCs (the areas under the concentration vs. time curves) in rat plasma. Cocaine had the highest incorporation rate understood and there was a 3600 fold difference between the ICR of cocaine and that of THCA, the lowest drug. The melanin affinity of these drugs was determined by incubating a test solution with melanin at 36 degrees C in the dark for 2 h. After incubation and centrifugation, the drug concentration in the filtrate was determined by GC/MS or LC. The drug most affinitive to melanin was cocaine, followed by benzphetamine, phencyclidine, methylenedioxymethamphetamine and LSD. The correlation coefficient between ICR and melanin affinity of the 20 drugs was 0.947 (0.949 excluding THCA). Lipophilicity was calculated from the retention times of HPLC according to Kaliszan's method. Although the correlation coefficient between ICR and lipophilicity was very low (0.201), it rose to 0.770 by removing only THCA. The combination of melanin affinity and lipophilicity brought about a higher correlation (0.979) with the ICRs. Our data also suggested that the higher ICRs of basic drugs than neutral or acidic ones are strongly related to the membrane permeability of the drug based on the pH gradient between blood (pH 7.4) and hair matrix (acidic).

Animals↗
PubMed2006

Drug screening of preserved oral fluid by liquid chromatography-tandem mass spectrometry.

BACKGROUND: Oral fluid is an alternative matrix with potential applications in road-side drug screening, work-place testing, drug treatment programs, and epidemiological surveys. Development of methods for extensive drug screening in oral fluid is warranted. METHODS: We developed a liquid chromatography- tandem mass spectrometry (LC-MS/MS) method for drug screening of preserved oral fluid collected with the Intercept collection device. Samples were prepared by liquid-liquid extraction with ethylacetate/heptane (4:1). LC-separation was achieved with an Atlantis dC18-column (2.1 x 50 mm, 3 microm particle). Mass detection was performed by positive ion mode electrospray LC-MS/MS and included the following drugs/metabolites: morphine, 6-monoacetylmorphine, codeine, buprenorphine, methadone, amphetamine, methamphetamine, 3,4-methylenedioxymethamphetamine, 3,4-methylenedioxyamphetamine, 3,4-methylenedioxyethylamphetamine, cocaine, benzoylecgonine, Delta-9-tetrahydrocannabinol, lysergic acid diethylamide, alprazolam, bromazepam, clonazepam, 7-aminoclonazepam, diazepam, N-desmethyldiazepam, 3-OH-diazepam, fenazepam, flunitrazepam, 7-aminoflunitrazepam, lorazepam, nitrazepam, 7-aminonitrazepam, oxazepam, zopiclone, zolpidem, carisoprodol, and meprobamat. RESULTS: Screening of 32 drugs was performed with a run time of 14 min. Within- and between-day relative CVs varied from 2.0% to 31.8% and from 3.6% to 39.1%, respectively. Extraction recoveries were >50% except for morphine (30%) and benzoylecgonine (0.2%). The concentrations of the lowest calibrator were 1 nmol/L (0.28 microg/L) to 500 nmol/L (68 microg/L), depending on the drug. CONCLUSION: The method allowed rapid and sensitive oral fluid screening for the most commonly abused drugs in Norway and will be used for a road-side survey of drug use in normal traffic.

Chromatography, High Pressure Liquid↗
PubMed2004

Rapid, transient, and dose-dependent expression of hsp70 messenger RNA in the rat brain after morphine treatment.

Induction of Hsp70 in the brain has been reported after intake of drugs of abuse like amphetamine and lysergic acid diethylamide. In this investigation, gene expression of Hsp70 and other heat shock genes in the rat brain was studied in response to morphine. Twenty milligrams per kilogram morphine intraperitoneally resulted in a marked induction of Hsp70 messenger RNA (mRNA) expression in the frontal cortex with a maximum increase of 13.2-fold after 2 hours. A moderate increase of Hsp27 mRNA expression (6.7-fold) could be observed after 4 hours, whereas mRNA expression of Hsp90 and of the constitutive Hsc70 did not exceed a mean factor of 1.8-fold during the 24 hours interval. The increase in Hsp70 mRNA was dose dependent, showing a significant elevation after doses ranging from 10 to 50 mg/kg morphine. In situ hybridization revealed enhanced Hsp70 mRNA expression mainly in cortical areas, in the hippocampus, in the paraventricular and supraoptic nuclei of the hypothalamus, in the locus coeruleus, as well in the pineal body. The double in situ hybridization technique revealed increased Hsp70 mRNA expression mainly in VGLUT1-positive neurons and to a lesser extent in olig1-positive oligodendroglia. Immunohistochemistry revealed a marked increase of Hsp70 protein in neuronal cells and blood vessels after 12 hours. In contrast to animal experiments, morphine did not increase Hsp70 mRNA expression in vitro in micro-opioid receptor (MOR1)-expressing human embryonic kidney 293 cells, suggesting no direct MOR1-mediated cellular effect. To exclude a body temperature-related morphine effect on Hsp70 mRNA expression, the temperature was recorded. Five to 20 mg/kg resulted in hyperthermia (maximum 40.6 degrees), whereas a high dose (50 mg/kg) that produced the highest mRNA induction, showed a clear hypothermia (minimum 37.2 degrees C). These findings argue against the possibility that Hsp70 induction by morphine is caused by its effect on body temperature. It may be speculated that increased expression of Hsp70 after morphine application protects brain structures against potentially hazardous effects of opiates.

Animals↗