[Etiology of psychoses of the acute, exogenous reaction type; diethylamide of lysergic acid, a toxic trace element with psychic effects].
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Ergot Alkaloids↗
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[Effects of diethylamide of lysergic acid on the psychic symptoms of schizophrenia; psychopathological study].
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Cardiovascular Agents↗
[Antagonistic effect of diethylamide of lysergic acid and of methylamphetamine on experimental catalepsy caused by 5-hydroxytryptamine; experimental research on dogs].
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Amphetamine↗
[Intoxication with mescalin and diethylamid of lysergic acid; autoexperiments with special consideration of a drawing test].
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Alkaloids↗
[Diethylamide of lysergic acid and carbohydrate metabolism].
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Carbohydrate Metabolism↗
The analysis of drug-induced tremor in mice.
An improved method of recording tremor in mice has been developed using a gramophone pick-up and a cathode ray oscillograph. Permanent records are made on 35 mm. film from which it is possible to determine qualitative differences in the tremor caused by various drugs. In addition, the severity of the tremor may be estimated quantitatively by a tremor index. The rate and variations in the rhythm and amplitude and in the tremor index have been determined for Tremorine (1,4-dipyrrolidin-1'-ylbut-2-yne), harmine, harmaline, 3-amino-1,1,3-triphenylpropan-1-ol and lysergic acid diethylamide. The incidence of side effects has also been noted.
Animals↗
THE EFFECTS OF DRUGS ON THE UPTAKE OF AMINES BY MAST CELLS.
Neoplastic mast cells, taken from an ascitic tumour in mice and incubated in vitro, took up (14)C-labelled 5-hydroxytryptamine and histamine from the medium. Uptake during the first hour gave an approximate measure of the initial rate. The amount of each amine taken up in this time was determined by bioassay and by radioactivity, the two methods giving similar results. The curves obtained by plotting initial rate of uptake against concentration in the medium suggested that the uptake of 5-hydroxytryptamine was by an active process and also by diffusion, whereas uptake of histamine was by diffusion only. The cells also took up (14)C-labelled (+/-)-noradrenaline and tryptamine, apparently by diffusion. The active uptake of 5-hydroxytryptamine was inhibited by lowering the temperature to 25 degrees C or by increasing the pH to 8.9, procedures which had little effect on histamine uptake. The effects of cocaine, imipramine, chlorpromazine, mepyramine, promethazine, phenoxybenzamine, lysergic acid diethylamide, bromolysergic acid diethylamide, methysergide, guanethidine, dichloroisoprenaline and pronethalol on the uptake of amines were examined. In general, any antagonist which inhibited uptake of 5-hydroxytryptamine had little effect on uptake of histamine, and vice versa. Possible ways in which these antagonists produce their effects on amine uptake are discussed. A high concentration of 5-hydroxytryptamine, of tryptamine or of noradrenaline inhibited uptake of histamine, but only tryptamine decreased uptake of 5-hydroxytryptamine. These results, together with those from experiments with antagonists, suggest that there are specific binding sites for 5-hydroxtryptamine in these cells.
Amines↗
Actions of certain amines on cerebral cortical neurones.
A number of derivatives of tryptamine and phenethylamine, and certain other compounds, were tested on neurones in the cerebral cortex of cats by iontophoretic release from micro-pipettes. The characteristic action of many of these compounds was a depression of the neuronal discharge initiated by synaptic activity or by the application of L-glutamate; imidazolylacetic acid, dopamine, ephedrine and ergometrine were particularly effective. Catechol amines, hydroxytryptamines and imidazolylacetic acid had a relatively quick and rapidly reversible action, not unlike that of gamma-aminobutyric acid, whereas ephedrine and derivatives of lysergic acid diethylamide caused a slower and more prolonged depression of the amplitude of spikes, rather like atropine. Several compounds, including 5-hydroxytryptamine, adrenaline and ergometrine, could also excite the same neurone when larger amounts were applied. A few substances, such as dopa and methylergometrine, had a predominantly excitant action.
Amines↗
The rat anococcygeus muscle and its response to nerve stimulation and to some drugs.
1. A new smooth muscle preparation, the rat anococcygeus muscle, is described. The muscle is paired, thin, consists of smooth muscle only and the muscle cells are organized in parallel bundles. It has a dense adrenergic innervation distributed throughout the muscle but apparently no cholinergic innervation. The muscles are easily isolated.2. The muscle contracts to noradrenaline, acetylcholine, furmethide, 5-hydroxytryptamine, but not to histamine. Isoprenaline produces contraction at high concentrations. The effects of noradrenaline and acetylcholine are blocked by phentolamine and atropine respectively. The response to isoprenaline is little affected by propranolol.3. The muscle contracts in response to field stimulation or stimulation of extrinsic nerves. This response is completely blocked by phentolamine but unaffected by hexamethonium or atropine.4. Guanethidine 10(-6)-5 x 10(-6)M blocks the motor response to nerve stimulation and potentiates that to noradrenaline. Higher concentrations of guanethidine raise tone. In the presence of raised tone, field stimulation produces an inhibitory response insensitive to hexamethonium but abolished by tetrodotoxin 2 x 10(-7) g/ml. This inhibitory response to stimulation can also be shown after other drugs which raise tone.5. The inhibitory response to nerve stimulation is not mimicked by acetylcholine, isoprenaline or ATP, nor blocked by atropine, phentolamine, phenoxybenzamine, propranolol, hexamethonium or lysergic acid diethylamide.
Acetylcholine↗
Serotonin release from brain slices by electrical stimulation: regional differences and effect of LSD.
Slices of rat brain which had accumulated tritiated serotonin either in vivo or in vitro were superfused and electrically stimulated. There occurred a marked release of the exogenous amine and, to a lesser extent, its deaminated metabolites, which varied with the region of brain tested and was inhibited by lysergic acid diethylamide.
Animals↗
Spectrofluorometric analysis of illicit drug samples, employing a corrected excitation spectrofluorometer.
Spectrofluorometry, because of its high sensitivity, has developed into one of the most useful analytical methods available to the forensic chemist for certain ilicit drug samples encountered in small amounts. The corrected excitation spectrofluorometer adds to the usefulness of this technique by generating more reproducible results with greater sensitivity. The excitation spectra are in better agreement with absorption spectra, and the need to recalibrate constantly with standard solutions in order to perform quantitative analysis can be minimized. Lysergic acid diethylamide and a fluorophore of morphine related drugs were examined employing a corrected excitation spectrofluorometer. Data is presented substantiating the advantages of a corrected instrument.
Hallucinogens↗
Studies on the mechanism of covalent incorporation of a lysergyl derivative to immunoglobulin peptides in vitro.
In vitro incubation of hyperimmune rabbit lymphoid cells with the hallucinogenic indole alkaloid, d-lysergic acid diethylamide (LSD), results in biosynthesis of modified, secretable immunoglobulin peptides. Modification involves covalent attachment of the lysergyl moiety to COOH-terminal portions of the peptides. Aalogous effects occur when cells are incubated in vitro in the presence of the non-hallucinogenic LSD analogue, d-lysergic acid, and N-[3H]-carboxymethyl-d-lysergamide. The phenomenon is reversed by tryptophan and is inhibited by puromycin and cycloheximide. In vitro attachment of the lysergyl moiety occurs in the presence of actinomycin D at levels which inhibit RNA synthesis. While LSD is not attached to intracellular tRNA, the drug binds to 80 S ribosomes from hyperimmune lymphoid cells with high affinity (K A equals 3.5 times 10-8 M-1). Similar binding occurs to nonimmune splenic ribosomes. Implications of these findings are discussed with respect to the degree of involvement of cellular protein translational mechanisms in the covalent attachment of the lysergyl moiety to low molecular weight immunoglobulin peptides.
Animals↗
Acute intravenous infusion in freely moving rats through the sagittal and transverse sinuses.
A technique is described which allows drugs to be injected intravenously using the junction of the sagittal and transverse sinuses as the point of entry into the venous system. The procedure is rapid and uses conventional stereotaxic techniques. Subsequent restraint of movement during drug infusion is minimal. Using this method, 15 mug/kg d-lysergic acid diethylamide produced an increase in acoustic startle amplitide within about 1-2 min which lasted for about 25 min.
Acoustic Stimulation↗
Lysergic acid diethylamine: mutagenic effects in Drosophila.
d-Lysergic acid diethylamide causes a significant increase in recessive lethal mutations in the X chromosome of Drosophila males after intraperitoneal injection of massive doses.
Animals↗
Discriminative stimulus properties of xylazine in rat: discriminability and effects of putative alpha-2 adrenoceptor agonists and antagonists.
In a first experiment, rats were trained initially to discriminate i.p. injections of 2.5 mg/kg of xylazine from saline in a two-lever, food-reinforced, fixed-ratio 10 drug discrimination procedure. The animals were then retrained on progressively lower doses of the training drug. The stimulus generalization gradient of xylazine was established each time the animals had reached criterion on successive training doses; the criterion required that lever selection be appropriate to the saline or xylazine injection on 10 consecutive sessions. The findings indicate the lowest xylazine training dose at which individual rats can reach criterion to range from 2.5 to less than or equal to 0.31 mg/kg; the median lowest discriminable dose was 0.89 mg/kg. The distribution of lowest discriminable dose accommodated a Gaussian shape. The slope of the xylazine gradient did not in a systematic manner vary as a function of training dose, and the ED50 value of xylazine was an almost constant fraction of training dose (1:2.0) at training doses ranging from 2.5 to 0.63 mg/kg. A second experiment examined the xylazine-like agonist and the xylazine-antagonist effects of clonidine, yohimbine, piperoxan and idazoxan in rats discriminating xylazine from saline at a training dose of 2.5 mg/kg. Clonidine produced generalization in all animals and antagonized the xylazine stimulus in one. Idazoxan produced near complete antagonism, and was generalized in one animal. Yohimbine and piperoxan produced magnitudes of agonist and antagonist effects that were intermediate between those of clonidine and idazoxan. Lisuride and d-lysergic acid diethylamide produced up to 71 and 29% generalization, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
Adrenergic alpha-Agonists↗
Hallucinogenic drugs are partial agonists of the human platelet shape change response: a physiological model of the 5-HT2 receptor.
We have assayed several phenylalkylamine and indolealkylamine hallucinogens, as well as structurally similar nonhallucinogens, for their effect on human platelet shape change, a physiological model for the central serotonergic 5-HT2 receptor. The hallucinogenic drugs lysergic acid diethylamide (LSD-25), N,N-dimethyltryptamine (N,N-DMT), 5-methoxy-N,N-dimethyltryptamine (5-MeODMT), 4-iodo-2,5-dimethoxyphenylisopropylamine (DOI), bufotenine, and mescaline all showed a characteristic 5-HT2 partial agonist effect on platelet shape change. Nonhallucinogens with structural similarity to hallucinogens did not share this profile. Lisuride, methysergide, and lysergic acid showed antagonism of 5-HT-induced shape change, but none were shape change agonists. Other "psychoactive" or mood-altering drugs (cocaine, amphetamine, phencyclidine) showed poor antagonism of 5-HT-induced platelet shape change. This work refines recent ideas that some of the behavioral effects of LSD-type hallucinogens in humans are due to their actions at 5-HT2 receptors and suggests that these hallucinogens are partial 5-HT2 agonists.
Blood Platelets↗
The mode of action of 5-hydroxytryptophan in facilitating a stretch reflex in the spinal cat.
1. Intravenous injection of 5-hydroxytryptophan (5-HTP) excites discharges of gamma motoneurones to extensor muscles of the hind limbs of decerebrate spinal cats and this occurs with a short latency (1-2 min). 2. 5-HTP also facilitates the stretch reflex in the spinal cat but, in contrast, there is a latency of about 10 min with a maximum action after 20 min. 3. Facilitation of the stretch reflex by 5-HTP still occurs when the gamma loop has been opened by cutting all ventral roots supplying the muscle. Thus excitation of gamma motoneurones by 5-HTP is not required for facilitation of the stretch reflex. 4. A possible contribution to the stretch reflex from the increased discharge of gamma motoneurones has been assessed. Selectively removing gamma activity rarely altered the reflex response to stretch and in only 3 out of 15 spinal cats could we conclude that gamma discharges contributed towards facilitation of the stretch reflex by 5-HTP; 5; Methysergide (0.25 mg/kg) blocked completely the facilitation of the stretch reflex caused by 5-HTP in the spinal cat but only partially antagonised the reflex in the decerebrate cat, even when injected intra-arterially close to the lumbar spinal cord. 6. Lysergic acid diethylamide (LSD) was found to mimic the actions of 5-HTP. It facilitated the stretch reflex and excited extensor gamma motoneurones in the spinal animal.
5-Hydroxytryptophan↗
Elucidation of LSD in vitro metabolism by liquid chromatography and capillary electrophoresis coupled with tandem mass spectrometry.
The in vitro metabolism of D-lysergic acid diethylamide (LSD) by human liver microsomes was investigated. Tandem mass spectrometric techniques, using precursor and neutral loss scans, were employed in the initial search for drug metabolites. The determination of LSD human liver in vitro metabolites was performed by high-performance liquid chromatography and capillary electrophoresis coupled with tandem mass spectrometry. Two new in vitro metabolites, lysergic acid ethylamide (LAE) and 2-oxo-LSD, were positively identified; their structures were established by comparing with reference standards. Several other possible in vitro metabolites detected were suggested to be mono- and trioxylated metabolites of LSD. The major metabolic route of LSD by human liver microsomes is deethylation. Some results with LSD-positive human urine are presented. Among the LSD-related compounds detected in human urine specimens, iso-LSD was present at the highest concentration, followed by nor-LSD and isonor-LSD. Low concentrations of LAE and iso-LAE were also found in these urine specimens.
Chromatography, Liquid↗