Konstitutionsaufklärung und Synthese von Psilocybin

Summary The structure of Psilocybin, the psychotropic active principle of the Mexican mushroomPsilocybe mexicana Heim, has been elucidated. Psilocybin is the phosphoric acid ester of 4-hydroxy-dimethyltryptamine. This structure was confirmed by total synthesis.     

Psilocybin,ein psychotroper Wirkstoff aus dem mexikanischen RauschpilzPsilocybe mexicana Heim

Summary The active principle ofPsilocybe mexicana Heim, a mexican mushroom with hallucinogenic properties, has been isolated in crystalline form. The compound has been given the namePsilocybin; it possesses indole characteristics and contains phosphorus. A second substance, closely related toPsilocybin but found only in traces, has been calledPsilocin.     

Action de la Psilocybine sur le cerveau du lapin

Summary Psilocybin, the by-product of which Psilocin] has been identified as 4-hydroxy-dimethyl-tryptamine (4-HTP) develops in the waking rabbit a marked activation of the somatic behaviour and of the electrical brain activity. This stimulating action is due to a depression of the mediothalamic recruiting and moderating system rather than to an activation of the reticular arousal system. The electrophysiological effects of 4-HTP are compared with those of 5-HTP.     

Zentrale vegetative LSD-Effekte

Summary d-Lysergic acid diethylamide (LSD 25) produces in rabbits a syndrome consisting of hyperthermia, hyperglycemia, mydriasis, pilomotor activation, cardiac acceleration etc. Analysis of these effects leads to the assumption of an increased sympathetic discharge induced by the central nervous action of LSD 25. Comparison of LSD 25 and reserpine shows opposite characteristics of these two drugs not only in the field of vegetative pharmacology but also concerning influence on psychic functions in man. The possibility should, therefore, be considered that an increased excitatory state of sympathetic centres by LSD 25 is a main factor in the pathogenesis of the well-known psychic disturbances produced by this amide in man.     

Osservazioni preliminari,chimiche e farmacologiche,sulla murexina

Summary (1) Murexine, a new choline derivative found in the hypobranchial body ofMurex trunculus, Murex brandaris, andTritonalia erinacea, was isolated as picrate, picrolonate, styphnate, flavianate, and reineckate. Some preliminary characteristics of these salts are given.(2) The murexine content of the median zone of the hypobranchial body ofMurex trunculus is extremely high: murexine picrate equivalents of 45–70 mg per g fresh tissue are commonly observed.(3) Murexine manifests intense nicotinic and curariform actions, but is practically wanting in any muscarinic activity.The central nervous system is strongly affected by the substance: at first stimulation seems to prevail, but later on, with larger doses, a deep depression regularly develops.In decapitated cats and dogs murexine causes a significant rise in blood pressure, which is due, at least partially, to a liberation of epinephrine from the adrenal medulla and from the adrenergic nerve terminals.On the enucleated eye of frogs andOctopoda the substance acts to cause mydriasis and expansion of the iris chromatophora.

---

---

V. Erspamer eF. Dordoni, Arch. int. Pharmacodyn.74, 263 (1947).     

The effect of L-dopa on pupillary diameter in mice

Summary Injection of L-dopa in mice produces dose-dependent mydriasis. Pre-treatment with peripheral dopa-decarboxylase inhibitors (carbidopa and benserazide) or with an alpha-adrenergic blocking agent (phentolamine) abolishes the pupillary dilation caused by L-dopa. Pretreatment with fusaric acid, an inhibitor of dopamine-beta-hydroxylase, also antagonizes the mydriatic effect of L-dopa. Thus, our results suggest that the mydriasis produced in mice following the injection of L-dopa is caused by its peripheral conversion to noradrenaline, which stimulates alpha-adrenergic receptors in the dilator iridis. There was no evidence that stimulation of specific dopaminergic receptors was involved.We are grateful to N. Rothschild, Head of Laboratory Animal Department, Sackler School of Medicine, for his help.     

Dämpfung des Kältezitterns durch Pentobarbital und Pethidin bei Ratten

Summary In rats, shivering was induced by cooling. Shivering started at 36.6°C in unanaesthetized rats and at 36.0°C in animals with light pentobarbital anaesthesia (5 mg/kg i.V.). Pethidine (2 mg/kg) lowered the onset of shivering in unanaesthetized rats to 35.3 °C and in anaesthetized animals to 33.0°C. The results suggest that the effect of pethidine upon shivering is potentiated by pentobarbital.     

Identifizierung von Psilocin

Summary Psilocin, a by-product of Psilocybin which is the active principle of hallucinogenic mushrooms, has been identified as 4-hydroxy-dimethyltryptamine.     

Splenic B-cell activation in lipopolysaccharide-non-responsive C3H/HeJ mice by lipopolysaccharide ofPorphyromonas gingivalis

Porphyromonas gingivalis 381 lipopolysaccharide (LPS) definitely exhibited mitogenic activity in purified B-cells, separated from spleens of LPS-responsive C3H/HeN mice and LPS-non-responsive C3H/HeJ mice by using a magnetic cell sorting system. The mitogenic activity induced byP. gingivalis LPS was incompletely inhibited by polymyxin B.P. gingivalis LPS also induced a higher production of interleukin-6 (IL-6) in splenic B-cells of C3H/HeN mice as compared withEscherichia coli LPS. Furthermore,P. gingivalis LPS, but notE. coli LPS, induced definite IL-6 production in C3H/HeJ mice.P. gingivalis LPS increased tyrosine, serine/threonine phosphorylation of proteins with various major induced bands in splenic B-cells of both C3H/HeN and C3H/HeJ mice. Additionally, radioiodinatedP. gingivalis LPS, similarly toE. coli LPS, bound to a 73-kDa protein on C3H/HeJ as well as C3H/HeN B-cells. ThusP. gingivalis LPS may activate B-cells of C3H/HeJ as well as C3H/HeN mice via the LPS-specific binding protein on the cells.     

Protective effect of Shigyaku-to,a traditional Chinese herbal medicine,on the infection of herpes simplex virus type 1 (HSV-1) in mice

The antiviral activity of Shigyaku-to (TJS-109), a traditional Chinese herbal medicine, was investigated in mice infected with herpes simplex virus type 1 (HSV-1). TJS-109 is a combination of the medicinal plant extracts fromZingiberis siccatum rhizoma,Aconiti tuber andGlycyrrhizae radix in a specific proportion. Mice infected with a 10 LD₅₀ dose of HSV-1 were treated with TJS-109 orally at doses of 1.25 to 20 mg/kg 2 days before, and 1 and 4 days after the infection. The treated groups had 80% (1.25 mg/kg), 40% (5 mg/kg) and 23% (20 mg/kg) mortality rates 25 days after the infection as compared with a 100% mortality rate in control mice treated with saline. When HSV-1 infected mice (recipients) received CD8⁺T cell fractions derived from spleens of mice treated with TJS-109 (donors), 70% of recipients survived, as compared with 0% survivors in the groups of mice treated with saline, B cell fractions, CD4⁺ T cell fractions or macrophage-enriched fractions prepared from the same donors. TJS-109 did not show any virucidal activities against HSV-1 or any virostatic activities on the growth of HSV-1 in Vero cells. These results suggest that TJS-109 protected mice exposed to lethal amounts of HSV-1 through the activation of CD8⁺ T cells.     

Is the ubiquitin-proteasome system impaired in Huntington’s disease?

Ubiquitylated inclusion bodies (IBs) found in Huntington’s disease (HD) postulate an impaired ubiquitin-proteasome system. However, this hypothesis remains controversial. In vitro-generated polyglutamine aggregates failed to inhibit purified proteasomes, while filamentous huntingtin aggregates isolated from mice resulted in inhibition. However, similarly isolated IBs did not, thus suggesting that IB formation is protective by sequestering smaller inhibitory aggregates. Accordingly, proteasome-activity assays in IB-containing mouse brain homogenates did not show decreased activity. On the contrary, some of the endoproteolytic proteasome activities increased, probably due to altered subunit composition. However, activity was found decreased in postmortem human HD tissue. Finally, evidence supporting the hypothesis was found in HD cell models expressing fluorescent ubiquitin-proteasome system reporters but not in retina of SCA-7 mice with similar reporters. In summary, it seems that mutant huntingtin, probably in intermediate aggregate forms, has the potential to inhibit proteasome activity, but the global status of the system in HD brain tissue is not yet fully elucidated.     

Studio farmacologico di un nuovo coleretico derivato dall'acidoα-cicloesil butirrico

Summary -(1-Hydroxy-4-phenyl-cyclohexyl)butyric acid (M. G. 4833) and-(1-hydroxy-3-phenyl-cyclohexyl) butyric acid (M. G. 4834) have been synthesized; both substances were endowed with choleretic activity.M. G. 4833 is the more active; it acts at lower doses and for a longer time than sodium dehydrocholate on rats, rabbits and dogs submitted to temporary fistulization of the bile-duct.     

Effects of the psychodysleptic drug psilocybin on visual perception. Changes in brightness preference

Zusammenfassung Die in gesunden, jungen Volontären durch Psilocybin hervorgerufene, reversible Veränderung der bevorzugten Helligkeit kann mit der Stabilität der Wahrnehmungspersönlichkeitsstruktur, nicht aber mit der mydriatischen Wirkung der Droge in Beziehung gebracht werden.     

Die postnatale Entwicklung der Bursttätigkeit im Bulbus olfactorius des Kaninchens

Summary An investigation of the olfactory burst activity was undertaken in rabbits during 1–8 days of life. The bursts are already present at the first postnatal day (frequency 18 c/sec, amplitude 23µV). The values of the adult animal are reached at 8 days.     

Bromocriptine/SKF38393 ameliorates islet dysfunction in the diabetic (db/db) mouse

Dysfunction of pancreatic islets plays a crucial role in the etiology of type II diabetes. Chronic hyperglycaemia or hyperlipidaemia may impair islet function. Previous studies by our laboratory have demonstrated that dopaminergic agonists ameliorated hyperglycaemia and hyperlipidaemia in obese and diabetic rodents. In the present study, we investigated the effect of a treatment with the dopamine D₂ /D₁ receptor agonists (bromocriptine/SKF38393, BC/SKF) on islet dysfunction in db/db mice. Our results show that a 2-week BC/SKF treatment markedly reduced hyperglycaemia and hyperlipidaemia, and significantly improved islet dysfunction demonstrated by an increase of secretagogue-stimulated insulin release from islets of db/db mice to levels observed in islets from lean mice. There was also a fourfold increase of insulin content in the pancreas of BC/SKF-treated db/db mice compared with that in untreated controls. The effect of BC/SKF on islet function cannot be mimicked in pair-fed animals. BC/SKF had no direct stimulatory effect on islet insulin secretion, suggesting BC/SKF treatment improved islet function via an indirect mechanism. This treatment markedly improved the abnormally elevated daily levels of corticosterone, blood glucose and plasma lipids, supporting the view that BC/SKF may affect the neuroendocrine system that in turn regulates peripheral metabolism and thereby improves islet function. Received 3 April 1998; accepted 27 April 1998     

Zur Frage des Umbaus parenteral zugeführter Serumeiweisskörper

Summary In the serum of rabbits,in vitro protein-synthesis takes place only in the presence of mitochondria (liver) and only with amino acids. Proteins synthesized in this manner are not identifiable with the serum proteins.     

On a rabbit hyperlipemia induced by a fungic galactomannane peptide

Summary I.v. injection into rabbits of a fungic galactomannane peptide isolated from the culture medium ofAspergillus oryzae induced the apparition, 20 h later, of an hypertriglyceridemia, with a concomittant decrease of about 70% of the post-heparin lipoprotein lipase activity. The same effect had been obtained earlier with a carbohydrate-rich fraction purified from a crude papain preparation. The 2 fractions are compared.     

Über Benzimidazolderivate mit starker analgetischer Wirkung

Summary A number of basically substituted benzimidazoles show a strong analgesic activity in mice, rats, rabbits, and dogs. Qualitatively they act very similarly to morphine and corresponding synthetic analgetics and the most active of these compounds are quantitatively superior to all analgetics hitherto described.     

Beta-carotene affects gene expression in lungs of male and female <Emphasis Type="Italic">Bcmo1</Emphasis><Superscript>−/−</Superscript> mice in opposite directions

Molecular mechanisms triggered by high dietary beta-carotene (BC) intake in lung are largely unknown. We performed microarray gene expression analysis on lung tissue of BC supplemented beta-carotene 15,15′-monooxygenase 1 knockout (Bcmo1 ^−/−) mice, which are—like humans—able to accumulate BC. Our main observation was that the genes were regulated in an opposite direction in male and female Bcmo1 ^−/− mice by BC. The steroid biosynthetic pathway was overrepresented in BC-supplemented male Bcmo1 ^−/− mice. Testosterone levels were higher after BC supplementation only in Bcmo1 ^−/− mice, which had, unlike wild-type (Bcmo1 ^+/+) mice, large variations. We hypothesize that BC possibly affects hormone synthesis or metabolism. Since sex hormones influence lung cancer risk, these data might contribute to an explanation for the previously found increased lung cancer risk after BC supplementation (ATBC and CARET studies). Moreover, effects of BC may depend on the presence of frequent human BCMO1 polymorphisms, since these effects were not found in wild-type mice.     

Inositol trisphosphate 3-kinases: focus on immune and neuronal signaling

The localized control of second messenger levels sculpts dynamic and persistent changes in cell physiology and structure. Inositol trisphosphate [Ins(1,4,5)P ₃] 3-kinases (ITPKs) phosphorylate the intracellular second messenger Ins(1,4,5)P ₃. These enzymes terminate the signal to release Ca²⁺ from the endoplasmic reticulum and produce the messenger inositol tetrakisphosphate [Ins(1,3,4,5)P ₄]. Independent of their enzymatic activity, ITPKs regulate the microstructure of the actin cytoskeleton. The immune phenotypes of ITPK knockout mice raise new questions about how ITPKs control inositol phosphate lifetimes within spatial and temporal domains during lymphocyte maturation. The intense concentration of ITPK on actin inside the dendritic spines of pyramidal neurons suggests a role in signal integration and structural plasticity in the dendrite, and mice lacking neuronal ITPK exhibit memory deficits. Thus, the molecular and anatomical features of ITPKs allow them to regulate the spatiotemporal properties of intracellular signals, leading to the formation of persistent molecular memories.