Beng T. Ho

Serotonin levels and platelet uptake during premenstrual tension.

Premenstrual tension was studied in 16 females, using both biochemical and psychological parameters during the pre- and postmenstrual phases. Uptake of serotonin (5-HT) and the levels of 5-HT in platelet-rich plasma and platelet-poor plasmas were determined. Degrees of distress experienced pre- and postmenstrually were quantified via the Moos menstrual distress questionnaire. The mean Vmax was significantly lower during the premenstrual (tension) phase (8.2 +/- 0.9 pmol/min) as compared to the postmenstrual (normal) phase (14.4 +/- 3.2 pmol/min). There was no significant difference in the Km values. A highly significant (p less than 0.001) reduction in the levels of 5-HT in platelet-rich plasma (-23.2%) and platelet-poor plasma (-19.1%) was found during the premenstrual phase. There were correlations between the kinetic parameters of 5-HT uptake and some of the Moos symptoms.

Marihuana: importance of the route of administration

Conventionally marihuana is used, or rather abused, by inhalation. In this respect it more closely resembles tobacco than alcohol with which it has most often been compared from a behavioural point of view. Yet, surprisingly enough, most experiments on the pharmacological, neurochemical, or behavioural effects of marihuana have relied on an intraperitoneal administration of extracts of cannabis or pure l-A9tetrahydrocannabinol (A9-THC), the major psychoactive constituent. In working with synthetic A9-THC (Idanpaan-Heikkila, Fritchie & others, 1969) we were impressed by its great water insolubility which led us to question just how well it might be absorbed via the various conventional routes of administration. TritiatedAg-THC with a specific activity of 250 pCi/mg was synthesized (Idanpaan-Heikkila, Fritchie & others, 1969) and administered to rats in Tween-80 as a suspension intraperitoneally and intravenously. Animals were killed at various times and autoradiographs prepared using the technique previously described (Ullberg, 1968 ; IdanpaanHeikkila, Vapaatolo & Neuvonen, 1968). 3H-A9-THC administered intraperitoneally remains in the abdominal cavity, with little absorption and distribution to other tissue, including the CNS (Fig. 1A and B). The same dose given intravenously was distributed throughout the body, including the CNS, within 5 min (Fig. 1C). Preliminary experiments also indicated good absorption and distribution after inhalation (Ho, Fritchie & others, 1970). Adiscrepancy exists between the known effective dose in man (100-250 pg/kg range inhaled) (Isbell, Gorodetzsky & Jasinski, 1967 ; Weil, Zinberg & Nelsen, 1968), and that used in most animal studies-10-25 mg/kg, and even as high as 00 mg/kg (intraperitoneally).

Behavioral Effects of Cocaine--Metabolic and Neurochemical Approach

Cocaine is known to be a local anesthetic and a potent CNS stimulant. Several reports indicate an increase in locomotor activity with low acute doses of the drug, and involvement of brain amines in this psychomotor stimulation has been proposed (Van Zwieten, Widhalm, and. Hertting, 1965; Groppetti, 1974).

Metabolism of harmaline in rats

Abstract The distribution and metabolic fate of [3H]harmaline-HCl were studied in rats. Thirty min after subcutaneous injection, high radioactivity was found in the small intestine, liver, adrenals, kidneys and lungs. A rapid turnover and elimination was evident after the first hour, as most of the tissues, except the liver, kidneys and intestines, had decreased nearly 50 per cent in levels of radioactivity. About 40 per cent of the harmaline was bound to human serum or rat serum proteins in vitro. The blood levels, however, were low at all times in vivo. The peak concentration in the brain occurred at 1 hr postinjection. The major route of excretion of harmaline and its metabolites was through the kidneys; a total of 62 per cent of the injected dose was excreted in the urine during 96 hr as compared to only 11·5 per cent in the feces over the same period. The major fate of harmaline in rats was demethylation to form harmalol, which was predominantly excreted as the glucuronide conjugate. Six to 10 per cent of the radioactivity was identified as the sulfate conjugate of harmol, which was formed by the dehydrogenation of harmalol. During the first 8 hr, unchanged harmaline in the urine amounted to about 25 per cent; however, this decreased to only 7 per cent during the 8–24 hr period.

Neuropharmacological study of Δ9- and Δ8-l-tetrahydrocannabinols in monkeys and mice

Abstract In monkeys, Δ8- and Δ9-THC were both active at 0.5 mg/kg. Animals receiving intravenously 0.5 and 2 mg/kg doses of both isomers exhibited changes in behavior. At 10 mg/kg, the animals became catatonic and uncoordinated. Both cannabinols caused a decrease in serotonin and norepinephrine in various discrete areas of the brain. It is possible that these neurochemical changes were related to the behavioral effects. In mice, after intravenous injection Δ8-THC exerted a greater effect on brain concentrations of serotonin and norepinephrine than the Δ9 isomer; although the latter is more potent behaviorally. Some differential effects of the two isomers on brain amine levels in specific areas might indicate that not only may there be a difference in potency between the two compounds, but that they might each have a qualitatively different spectrum of psychopharmacological action.

Metabolism of 6-Methoxytetrahydro-β-Carboline in Rats

1. Thirty minutes after intraperitoneal injection of 6-methoxytetrahydro-β-carboline, rapid uptake by the lungs, liver, kidney, adrenals, brain and spleen was observed, and by 6 h the radioactivity in most tissues except liver and testes had decreased to less than half of the max. values.2. Approximately 71% of the administered dose was found in the urine within 72 h, as compared to a total of 9% that appeared in the faeces over the same period of time. After oral administration, rats excreted 64 and 14% of the administered dose in 72 h in the urine and faeces, respectively.3. The major metabolic pathway for 6-methoxytetrahydro-β-carboline was hydroxylation of the 7-position and demethylation of the 6-methoxy group. The two metabolites, 6-methoxy-7-hydroxytetrahydro-β-carboline and 6-hydroxytetrahydro-β-carboline were excreted in urine in nearly equal amounts, almost entirely as glucuronide and sulphate conjugates with the latter predominating. The presence of conjugates of the two metabolites in the bile...

Catechol-O-methyltransferase and catecholamines in anxiety and relaxation

Levels of anxiety, plasma epinephrine and norpinephrine, and red blood cell (RBC) catechol-O-methyltransferase (COMT) activity were measured before and after 4 weeks of relaxation training in a group of 15 drug-free, anxious subjects and at a similar interval in a group of 15 drug-free, healthy controls. The index group showed significant decreases in levels of anxiety and plasma epinephrine and norepinephrine after treatment. No changes were observed in the control values. RBC COMT did not show any significant differences in activity between the index and control groups and between the pre- and posttreatment values. Similarly, COMT activity levels failed to correlate with levels of anxiety and catecholamines before or after treatment. These findings indicate that anxiety is unlikely to have an effect on RBC COMT activity, whereas it has a direct effect on plasma catecholamines.

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.

Relation of pharmacological and behavioral effects of a hallucinogenic amphetamine to distribution in cat brain.

The hallucinogen 2,5-dimethoxy,-4-methylamphetamine, also known as STP, accumulates in specfic areas of cat brains. The unchanged compound was detected in the brain for at least 6 hours, whereas its behavioral effects lasted for about 4 hourS. The coincidental pharmacological and behavioral effects of the compound apparently indicate a relation between the anatomical distribution and action.

Correlation between plasma cortisol and CSF catecholamines in endogenous depressed dexamethasone nonsuppressors

Nineteen endogenous depressive in-patients (13 with major depression and 6 with bipolar disorder-depressed) and 10 other patients with dysthymic disorder serving as the control group were given the dexamethasone suppression test (DST, 1 mg/subject). The results showed that the DST sensitivity in endogenous depressives was 73.7% and the specificity was 90%. After the patients were treated daily for 6 weeks with 150-200 mg imipramine, 88.9% of those endogenous depressive patients who previously had a positive DST response exhibited a negative response. Moreover, a significantly negative correlation was found between the CSF norepinephrine level and the pre-dexamethasone 4 p.m. plasma cortisol level in those endogenous depressed patients who had a positive DST response. Pre-treatment data also showed that the 4 p.m. plasma cortisol had a significant negative correlation with CSF dopamine. These findings suggest that endogenous depression with positive DST could be related not only to a lower norepinephrine level, but also to a lower dopamine level.