Distribution and fate of14C-labeled lysergic acid diethylamide (LSD 25) in the animal body

Zusammenfassung Es wird die Verteilung, Umwandlung und Ausscheidung von intravenös verabreichtem¹⁴C-markiertem Lysergsäurediäthylamid (LSD) an der weissen Maus untersucht.Praktisch die ganze, in Form von¹⁴C-markiertem LSD applizierte Radioaktivität verschwindet innerhalb weniger Minuten aus dem Blut, um nach 10–15 min in den meisten Organen ein Maximum zu erreichen, aus denen sich die Radioaktivität in den nächsten Stunden langsam wieder verliert. Im Dünndarm steigt die Aktivität in den ersten 2 h zu einem Maximum an, das ungefähr 50% der totalen Dosis entspricht. Die radioaktive Substanz bewegt sich mit dem Darminhalt, und 2–3 h später wird der grösste Teil der Aktivität im Colon gefunden.Durch Extraktionsversuche unter Zusatz von inaktivem LSD wird gezeigt, dass der grösste Teil des LSD im Organismus chemisch verändert wird. Drei verschiedene, wasserlösliche radioaktive Abbauprodukte werden durch ihreR _f-Werte charakterisiert.     

Metabolites of LSD and ergometrine

Zusammenfassung Vorläufige Untersuchungen über die Verwandlung von LSD und Ergometrin bei der Ratte zeigen, dass von beiden Substanzen zwei Hauptprodukte gewonnen werden. Beide Metaboliten von LSD antagonisieren 5-HT am isolierten Rattenuteruspräparat; es scheint sich um hydroxilierte und konjugierte Derivate des LSD zu handeln.

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This work was supported by grants from Burroughs Wellcome, Aus. (M. S.) and Drug Houses of Australia (J. P.).     

Ineffectiveness of lysergic acid diethyl amide−25 (LSD) on altering Na-K currents in squid giant axon

Zusammenfassung Nachweis, dass Lysergsäurediäthyl-amid^–25 (LSD) die Ionenströme von Na und K im Riesen-axon des Tintenfisches auch in hohen Konzentrationen nicht beeinflusst.     

Evidence of catecholamine mediation in the ‘Aberrant’ behaviour induced by lysergic acid diethylamide (LSD) in the rat

Zusammenfassung Der Einfluss verschiedener Pharmaka auf das durch LSD hervorgerufene bizarre Verhalten der Ratte wurde untersucht. Die Resultate zeigen, dass - und -Blocker sowie -Methyltyrosine eine starke Hemmung dieses Verhaltens erzeugen, im Gegensatz zu den Serotonin-Antagonisten Deseril, BOL-148 und Parachlorphenylalaninen, die nur schwache oder keine Hemmung hervorrufen. Es wird gefolgert, dass das bizarre Verhalten durch Wirkung von LSD an Katecholaminstrukturen hervorgerufen wird. Die Wirkung von 4 psychotropen Pharmaka am bizarren Verhalten wird im Rahmen dieser Hypothese diskutiert.     

Interaction of serotonin and lysergic acid diethylamide (LSD) in the central nervous system

Zusammenfassung Serotonin (5-Oxytryptamin) wirkt bei der Maus als mildes Sedativum und steigert den hypnotischen Effekt von Evipan deutlich. Diese Wirkungssteigerung kann durch Lysergsäure-diäthylamid (LSD) antagonisiert werden. Dieser Befund stimmt mit der Ansicht überein, dem Serotonin komme eine physiologische Rolle im Gehirn zu und dass LSD möglicherweise durch antagonistische Wirkung gegenüber Serotonin Psychose verursachen kann.     

LSD induced chlorophyll mutations in barley

Summary In earlier reports, LSD was found to induce extensive chromosomal aberrations in barley. With the same dose it is now observed that LSD is potent in the induction of chlorophyll mutations. This may be the first evidence that the drug induces gene mutations in plants.Acknowledgent. We are grateful to Dr H.K. Jain, Indian Agricultural Research Institute, for his interest and guidance.     

The biliary excretion of [3H] lysergic acid diethylamide in Wistar and gunn rats

Summary The biliary excretion of [³H] LSD was studied in Wistar and homozygous Gunn rats. In Wistar rats approximately 46% of the given dose was recovered from bile in 2.5 h whilst in the homozygous Gunn rat 26% was recovered in the same time period. In both strains the main metabolites were glucuronides.     

Changes in the liver protein pattern due to lysergic acid diethylamide (LSD)

Riassunto Mediante elettroforesi in fase libera è stato studiato il protiogramma epatico durante l'intossicazione con dietilamide dell'acido lisergico (LSD) nel ratto albino.Si sono osservate profonde modificazioni del quadro le quali sonto completamente reversibili.     

RNA in planarians (Dugesia lugubris) treated with LSD

Riassunto Se si mantengono Planarie (Dugesia lugubris) per otto giorni in una soluzione di LSD (0,02 mg/ml), si nota un aumento di RNA nella parte cefalica del soggetto rispetto ai corpi e anche rispetto alle teste dei controlli. Anche l'incorporazione di uridina triziata segue lo stesso andamento. Vengono proposte alcune ipotesi.     

The subcellular distribution of lysergic acid diethylamide in the rat brain

Résumé Quinze min après une injection i.p. de LSD, près de 48% de la drogue présente dans le cerveau fut trouvée dans le surnageant, 20% dans la fraction nucléaire, 15% dans la fraction synaptosomale, 6% dans la fraction microsomale, 5% dans la fraction myélinique et près de 1,7% dans la fraction mitochondriale. Les fractions synaptosomale et mitochondriale sont presque saturées en LSD lors d'une injection de 10 mg/kg de LSD.

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Acknowledgment. I thank Dr.J. Knopp for his help with the spectrophotoflourometric analysis.     

Lysergic acid diethylamide affects blood flow to specific areas of the conscious rat brain

Zusammenfassung Die i.v. Verabreichung von LSD an Ratten steigert den Blutkreislauf im Hirnstamm sowie im frontalen und parietalen Cortex selektiv. Es wurden durch 6-Nor-LSD, 2-Methyl-LSD und ^{8, 9}-LSD weder wahrnehmbare Verhaltensänderungen noch Änderungen des regionalen Blutkreislaufs verursacht.     

Lack of pressor effect of dopamine in the pentobarbital-anesthetized rat

Summary The blood pressure and heart rate responses to intravenous dopamine infusion at 2.5, 5.0 and 10.0 g·min^–1·100 g^–1 were studied in conscious and pentobarbital-anesthetized Sprague — Dawley rats. In the conscious rats, dopamine caused a significant dose-related increase in the mean arterial blood pressure which was abolished in the anesthetized rats. The heart rate increased significantly only at the highest dose infused. The responses to equipressor doses of noradrenaline (40 ng·min^–1·100 g^–1) and phenylephrine (1.0 g·min^–1·100 g^–1) were also suppressed in the anesthetized rats. The results suggest that pentobarbital anesthesia depresses the blood pressure response to dopamine infusion in the rat through a depression of activation of alpha-adrenoceptors.16 June 1986     

LSD effects on signal-to-noise ratio and lateralization of visual cortex and lateral geniculate during photic stimulation

Résumé L'administration de LSD augmente les effets de la stimulation contralatérale, la latéralisation et le rapport signal-sur-bruit. Ces résultats sont en accord avec le modèle de fonctionnement cérébral considéré comme un détecteur cohérent en parallèle.     

Metabolism of 1,3,7-trimethyldihydrouric acid in the rat: New metabolic pathway of caffeine

Summary [1-CH₃-¹⁴C] 1,3,7-trimethyldihydrouric acid which, in quantity, is the most important caffeine metabolite, was isolated and purified from the urine of rats fed with [1-CH₃-¹⁴C] caffeine. The oral administration of this metabolite to rats showed that 1,3,7-trimethyldihydrouric acid was excreted unchanged in urine and was therefore an end product of caffeine metabolism. This result implies a new metabolic pathway of caffeine.     

Human platelet 5-hydroxytryptamine receptors: binding of [3H]-lysergic acid diethylamide (LSD). Effects of chronic neuroleptic and antidepressant drug administration

Chronic treatment with phenothiazines and thioxanthenes has been found to enhance 5-HT-induced aggregation of human platelets. A method has been developed to study 5-HT2 receptor binding sites on platelets utilising [3H]-LSD and more recently 125I/LSD. Results are presented which suggest that the LSD binding site is indeed the 5-HT2 binding site and that the LSD binding characterises the specific receptor responsible for 5-HT-induced shape change and aggregation. In a group of patients receiving phenothiazines or thioxanthenes, the Bmax of LSD binding was increased. The mean binding affinity was decreased possibly due to a persistence of neuroleptic in the platelet membrane preparation. Analysis showed that this was not the reason why the mean binding capacity was increased. The results show that chronic phenothiazine and thioxanthene delta treatment 'up-regulates' platelet 5-HT2 binding sites and that this may be accompanied by increased sensitivity to platelet aggregation by 5-HT. In normal subjects desipramine treatment increased the Bmax of platelet LSD binding and this was accompanied by an increased prolactin response to tryptophan which is thought to be mediated by central 5-HT function.     

Diabetes alters drug metabolism-in vivo studies in a streptozotozin-diabetic rat model

Summary The influence of experimental streptozotozin-induced diabetes on hepatic drug metabolism in vivo has been studied in rats, using¹⁴CO₂-exhalation after¹⁴C-aminopyrine injection. Male diabetic rats showed a decreased (–18%), females an increased (+19%)¹⁴CO₂-exhalation compared to controls, indicating altered hepatic drug metabolism due to diabetes.     

High affinity binding of 5-hydroxytryptamine to some membrane preparations from cattle brain. Relationship to lysergic acid diethylamide (LSD)]

5 hydroxytryptamine binds to crude brain membrane preparations with two different affinities (KD = 1 to 2 X 10(-9) M for the highest, 1 to 2 X 10(-8) M for the lowest). LSD also binds with two affinities (KD = 3 to 4 X 10(-9) M and KD = 2 to 3 X 10(-8) M). Subcellular distribution of these sites shows that binding involves the two binding affinities in microsomal membranes but solely the high affinity binding sites are present in purified synaptosomal membranes. High affinity sites for 5 HT and for LSD are different as no direct competitive inhibition is observed in that case. On microsomal membranes, direct relationship occurs between low affinity binding for 5 HT and high affinity binding for LSD.     

Electrocorticographic activity induced by gamma hydroxybutyrate in the rat during ontogenesis

Summary GHB at a dose of 200 mg·kg^–1 i.p. elicited groups of slow waves with a frequency of 4–5 Hz in both frontal and occipital ECoG leads in adult rats. In 25- and 18-day-old rats similar slow wave activity became continuous and exhibited a clear-cut maximum in the frontal regions. In 15- and 12-day-old animals slow wave activity was also registered in the frontal region but it was organized into short groups of unstable frequency. No ECoG effects of GHB could be found in 9-day-old rats.     

Allotransplantation of rat parathyroid glands: Effects of organ culture and transplantation into the adrenal gland

Summary Allotransplantation of fresh, 1 or 2 week cultured parathyroid glands from Wistar rats (AgB²) to Fischer rats (AgB¹) resulted in prompt rejection of the transplant in the muscle site; whereas transplantation into the adrenal site offered slightly prolonged survival, suggesting that the latter is a privileged transplantation site.Acknowledgments. The authors thank Mrs Barbara Lovett for her secretarial assistance.