Mauno M. Airaksinen

Platelet serotonin uptake sites increased in drinkers of ayahuasca

The binding of [3H]citalopram to the platelet 5-hydroxytryptamine (5-HT) transporter was measured in a group of healthy male drinkers ofayahuasca, a psychoactive sacrament indigenous to Amazonia, and a group healthy male controls. An increased number of binding sites (Bmax) in the platelets of ayahuasca drinkers was found, while the dissociation constant (Kd) remained the same for both groups. If indicative of neuronal 5-HT uptake activity, these results would suggest a decreased concentration of extracellular 5-HT, or a response to increased production and release of 5-HT. Such changes in 5-HT synaptic activity, in this case, should not be misinterpreted as an indication of developing neurological or psychiatric illness.

Myoglobinuria after intermittent administration of succinylcholine during halothane anesthesia.

After the intermittent administration of succinylcholine to 24 ophthalmic patients during halothane anesthesia, 2 certain (immunochemically verified) and 5 probable cases of myoglobinuria were found. In all these patients the serum activity of creatine kinase was also elevated. These findings are interpreted as signs of probable museular injury. It is recommended that intermittent administration of succinylcholine during halothane anesthesia should be abandoned.

Biological activities of some 5-substituted N,N-dimethyltryptamines, α-methyltryptamines, and gramines

SummaryThree series of derivatives of N,N-dimethyltryptamine, α-methyltryptamine and gramine bearing substituents of varying electronic nature on the C-5 position were tested for acute toxicity, effect on barbiturate sleeping time, antireserpine effect, swim maze, variable interval conditioned behavior, and inhibition of monoamine oxidase. No correlation could be made between the electronic effects and their pharmacological activities. It was thus suggested that there exist different pharmacological receptors for the tryptamines and gramines.

Glucuronidation of 5-hydroxyindole derivatives in vitro.

Abstract Glucuronidation of 5-hydroxytryptophan- 14 C (5HTP), 5-hydroxytrypta-mine- 14 C creatinine sulphate (5HT), 5-hydroxytryptophol (5HTOH), 5-hydroxyindole-acetic acid (5HIAA) and p -nitrophenol was studied in liver, kindey and intestinal homogenates of Sprague-Dawley and Wistar rats. 5-Hydroxyindoles were acceptors of glucuronyl radicals in the following decreasing order: 5HTOH, 5HT, 5HTP, 5HIAA; and p -nitrophenol was 10–15 times more active an acceptor than 5HT. Formation of 5HT glucuronide was found also when 5HTP was the substrate and, correspondingly, glucuronides of 5HTOH and/or 5HIAA were formed when 5HT was incubated. Sodium edetate (EDTA) increased the glucuronidation especially in the intestine. EDTA and α-methyldopa decreased the formation of 5HT glucuronide from 5HTP, and EDTA as well as pheniprazine decreased that of 5HTOH and/or 5HIAA glucuronides from 5HT. Judged from the EDTA experiments the most intense glucuronidation occurred in the intestinal mucous membrane of Sprague-Dawley rats and in the liver of Wistar rats. The glucuronidation of 5-hydroxyindoles ran parallel to that of p -nitrophenol in different tissues of both strains as well as in young and adult rats.

Estrus cycle in rats: The role of serotonin and norepinephrine

p-Chlorophenylalanine, an inhibitor of seratonin synthesis, greatly increased the incidence of estrus when chronically administered to rats. Win 18, 506 (oxypertine), a centrally active sympatholytic drug which also decreased the norepinephrine content of brain, had the opposite effect. The finding that both oxypertine and p-chlorophenylalanine were without effect in pinealectomized rats suggests that the action of these drugs may be via the pineal where the formation of inhibitory 5-methoxyindoles is normally inhibited by adrenergic innervation.

Formation of tetrahydroharman (1-methyl-1,2,3,4-tetrahydro-beta-carboline) by Heucobacter pylori in the presence of ethanol and tryptamine

Helicobacter pylori contains alcohol dehydrogenase which oxidizes ethanol to acetaldehyde. In the present study, H. pylori cytosol was incubated in a buffered media at pH 6.0 and 7.4 in the presence of ethanol and tryptamine. Under these conditions, tetrahydroharman (1-methyl-tetrahydro-beta-carboline) was produced as a condensation product of tryptamine and acetaldehyde. At pH 6.0, 20.60 +/- 5.00% of the added tryptamine was converted to tetrahydroharman, while 27.00 +/- 4.80% (mean +/-SD) was converted at pH 7.4. Similar reactions between acetaldehyde and other dietary amines seem likely. Such biogenic alkaloids, if formed in vivo, might contribute to the dysphoric effects of alcohol.

The effect of chronic treatment with peripheral benzodiazepine receptor ligands on behavior and GABAA/benzodiazepine receptors in rat.

SummaryRats were twice daily (2 × 10 mg/kg, i.p.) treated for three weeks with the peripheral benzodiazepine (BZ) receptor ligands Ro 5-4864 (4′-chlorodiazepam) and PK 11 195 (1-(2-chlorophenyl)-N-methyl-N-(1-methylpropyl)-3-isoquinoline-carboxamide). After the first injection there were no differences between the drug-treated and control animals in behavioral tests. After 10 days treatment, the number of sniffings was increased in Ro 5-4864-treated rats. After the last injection, sniffings and ambulations were decreased in PK 11 195-treated animals. The number of rearings and groomings remained unchanged throughout the treatment, and there were no changes in the results in the elevated plus-maze test. Apparently these compounds are devoid of anxiolytic and anxiogenic effects at moderate doses.The effect of 72 a h withdrawal from the above mentioned chronic treatment on peripheral and central BZ receptors as well as on GABAA receptors was studied with receptor binding techniques using 3H-Ro 5-4864, 3H-flumazenil and 3H-muscimol, respectively, as ligands. The number of GABAA and central BZ receptors was lower after Ro 5-4864 treatment, as was the effect of progesterone-induced stimulation of 3H-muscimol binding. The number of peripheral BZ receptors was decreased after Ro 5-4864 and PK 11 195 treatments in the olfactory bulb but not in the cerebral cortex.The chronic treatment with peripheral BZ receptor ligands ] Ro 5-4864 and PK 11 195 produced only little behavioral effects. Ro 5-4864, often presented as an agonist of peripheral BZ receptors, was behaviorally inactive. PK 11 195, often considered to be an antagonist of Ro 5-4864 developed a small sedative action during chronic treatment. The withdrawal from chronic treatment with these ligands similarly affected peripheral BZ receptors but only Ro 5-4864 affected GABAA/BZ receptor complex in the CNS.The present data support the idea that Ro 5-4864 has independent of peripheral BZ receptors effects on GABA, receptors while PK 11 195 is rather a partial agonist than antagonist of peripheral BZ receptors.

Radioautographic study on the distribution of oxypertine (Win 18,501) in mice and cats

SummaryThe distribution of i.v.-injected tritiated oxypertine was studied in mice and cats by an autoradiographic technique. The compound rapidly accumulated in the lung, kidney, liver, adrenal medulla and brain. Later on the radioactivity concentrated also in bone marrow, pancreas and salivary glands, and still more in the gall-bladder and gastro-intestinal contents. The adrenal medulla, liver and kidney retained their activity for a long time. The hippocampus, thalamus and cerebral cortex were the most active sites in the brain. Oxypertine passed the placental barrier and was found especially in the foetal membranes and placenta and in the liver and gut contents of the foetus.

Distribution and fate of 3H-Oxypertine in rats

Abstract The distribution and fate of tritiated oxypertine (Win 18,501-T) was studied in rats after intravenous administration. Brain and lung became radioactive in 10 min, but the activity quickly disappeared. The highest activities at times between 30 min-72 hr after administration were found in glandular tissues. Lacrimal and salivary glands, liver and kidney showed a high activity, and even in testes, vesicula seminalis and the walls of stomach and duodenum the concentrations were higher than in blood. In adrenals the radioactivity increased during the first 3 hr and at later times the adrenals were the most active tissue of the rat. In nonanaesthetized rats half the radioactivity was excreted in 18 hr. Most was found in urine, about 20 per cent in faeces and very small amounts in expired air. In anaesthetized rats bile contained more radioactivity than urine during the first 8 hr but later the proportion in urine increased. About 4 per cent of the dose was excreted in the gastric juice in 24 hr. Practically all the radioactivity in bile and urine was in the form of metabolites of oxypertine. Chromatographic and mass spectrometric analysis indicated that oxypertine is metabolized by O -demethylation and by alcoholic and phenolic hydroxylations. Dihydroxylated derivatives were found as major metabolites. The alcoholic metabolites were partly oxidized further to the corresponding acid and the demethylation product was found as a chinone imine.

Metabolites of labelled 5-hydroxytryptamine in urine and bile of rats after various routes of administration

Abstract Urinary metabolites of 14 C-labelled 5-hydroxytryptamine (5HT) were studied in hydrated rats after subcutaneous (s.c.), rapid and slow intravenous (i.v.), and oral administration. Total excretion after an oral dose was about half of those after parenteral doses. Chromatography of an 8 hr urine sample showed that O-conjugates of 5HT (mainly O-glucuronide, less O-sulphate) were the main metabolites after oral administration and that smaller quantities of the conjugates were excreted after s.c. than after i.v. administration. Conversely small amounts of 5-hydroxyindoleacetic acid (5HIAA) were excreted after oral administration and also less after i.v. than after s.c. injection. O-conjugates of 5HIAA, also were excreted in smaller amounts after oral than after parenteral administrations. In anaesthetized rats the bile also was collected after s.c. and oral doses of 14 C-5HT. It contained a small amount of radioactivity, which seemed to be due to O-conjugates of 5HT and 5HIAA.