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Biomedical subjects

J Halmekoski

Publications and source records attributed to J Halmekoski.

14 recordsLinked to original sources
PubMed1985

Comparison of central nervous system actions of taurine and N-pivaloyltaurine.

N-Acetyl, N-propionyl, and N-pivaloyl derivatives of taurine were synthesized by applying a modified Schotten-Bauman method starting from taurine and using the corresponding acid chloride or acid anhydride for direct acylation reactions. The central nervous system actions of these lipid soluble taurine derivatives, which were presumed to pass the blood-brain barrier, were studied and compared to those of taurine in mice. A large dose (15 mmol/kg) of intraperitoneally administered taurine lengthened the pentobarbitone induced sleep by 30%. N-Pivaloyltaurine was 45 times more potent but not more effective than taurine. Neither N-acetyl- nor N-propionyltaurine lengthened the pentobarbitone induced sleep in doses up to 3 mmol/kg. Intraperitoneally administered N-pivaloyltaurine depressed the locomotor activity in a smaller dose and for a longer period than taurine. However, when administered intracerebroventricularly neither N-acetyl- nor N-pivaloyltaurine altered the locomotor activity in three times larger dose than in which taurine clearly depressed it. Intraperitoneally administered N-pivaloyltaurine decreased the rectal temperature slightly more than taurine, whereas intracerebroventricularly administered taurine was clearly more potent in inducing hypothermia than its acyl derivatives. Intraperitoneally administered N-pivaloyltaurine was about three times more potent than taurine in increasing the striatal concentration of dopamine. Intraperitoneally administered N-pivaloyltaurine only in a very large dose (3 X 15 mmol/kg) slightly and transiently increased the cerebral taurine concentration. Carboxylesterase inhibition by bis-p-nitrophenyl phosphate (BNPP) did not modify this increase. Furthermore, BNPP pretreatment modified neither the hypothermic nor the striatal dopamine concentration elevating effects of N-pivaloyltaurine. Our results suggest that N-pivaloyltaurine possesses taurine-like pharmacological actions. It is not converted to taurine to produce these actions. When administered intracerebroventricularly it is less potent than taurine. However, when administered intraperitoneally it is more potent than taurine because it seems to pass the blood-brain-barrier more easily than taurine. Thus N-pivaloyltaurine could be used to study the behavioural and other central nervous system actions of taurine.

Animals↗
PubMed1982

Cardiovascular and ventilatory effects of taurine and homotaurine in anaesthetized rats.

The cardiovascular and ventilatory effects of intravenous (i.v.) or intracerebroventricular (i.c.v.) injections of the aminosulphonic acids, taurine and homotaurine, were studied in urethane-anaesthetized rats. Taurine induced dose-dependent falls in blood pressure, heart rate and ventilatory tidal volume on i.c.v. but not on i.v. administration. Homotaurine induced dose-dependent hypotension and bradycardia when given i.v. and i.c.v. It was, however, more effective when injected i.c.v., and the decrease in ventilatory tidal volume occurred after i.c.v. administration of homotaurine only. Pretreatment of the rats with reserpine attenuated both the hypotensive and bradycardic responses to taurine and homotaurine. Atenolol and atropine both partly inhibited, and in combination totally abolished, the bradycardic effects of taurine and homotaurine without changing the hypotensive responses to these compounds. The ventilatory responses were not significantly changed by any of the pretreatments. The results suggest that the central cardiovascular effects of taurine and homotaurine are mediated both by a decrease in sympathetic tone and an increase in the parasympathetic tone.

Animals↗
PubMed1979

Acute dapsone intoxication: a case with prolonged symptoms.

A 45-year-old man ate about 10 gm of dapsone (DDS). After initial vomiting marked methemoglobinemia with cyanosis, headache, and confusion developed. Methemoglobinemia subsided 7 days after ingestion when the concentrations of DDS and monoacetyldapsone (MADDS) were at the therapeutic level. Signs of hemolysis appeared on the third day after DDS ingestion, the hemolysis being maximal more than one week after ingestion. The initial disappearance of DDS and MADDS was slow, the apparent half-lives being 88 and 67 hr, respectively. Peroral activated charcoal seemed to shorten the half-lives of DDS and MADDS markedly. This result supports the concept of the enterohepatic cycle of dapsone and recommends the use of activated charcoal for several days in acute poisonings caused by DDS.

Acetylation↗
PubMed1977

Effect of acetyl derivatives of some sympathomimetic amines on the blood pressure of the rat.

The effect of five sympathomimetic amines and some of their acetyl derivatives on the blood pressure of the rat was determined on the left carotid artery. After pretreatment with chlorisondamine (1 mg/kg subcutaneously) the blood pressure rise by sympathomimetic amines and their acetyl derivatives was compared with that of adrenaline. If the potency of adrenaline is specified as 100, the potencies of the other drugs are phenylephrine (metaoxedrinum, NFN) 37, tyramine 1.1, O-acetyltyramine 0.52, amphetamine 0.50, O-diacetylphenylephrine 0.25, ephedrine 0.23, O-acetylephedrine 0.02, N-acetylphenylephrine 0.01. The effects of N-acetyltyramine, N-acetylephedrine and N-acetylamphetamine are even weaker. Reserpine 5.0 or 0.05 mg/kg intraperitoneally 24 hours before the experiment increased the blood pressure rise by the directly acting sympathomimetic amines and their acetyl derivatives, but decreased the effects of the indirectly acting drugs. After treatment with phenoxybenzamine (2 mg/kg intraperitoneally), adrenaline exhibited the greatest blood pressure decrease and the effects of the other drugs in descending order: orciprenaline, O-acetyltyramine, phenylephrine, ephedrine, amphetamine, O-diacetylphenylephrine and O-acetylephedrine. Tyramine did not show any blood pressure decrease. The blood pressure decrease by sympathomimetic amines and by their acetyl derivatives was probably due to beta-receptor stimulation because it was prevented by propranolol. The N-acetyl derivatives recembled their parent drugs with regard to the immediate onset and short duration of their effects. The O-acetyl derivatives exhibited slower onset and longer duration of effect than their parent drugs. Physostigmine-pretreatment diminished the rise in blood pressure by O-acetyltyramine, but the effect of tyramine remained unchanged.

Amphetamines↗
PubMed1977

Release of platelet 5-hydroxytryptamine by some anorexic and other sympathomimetics and their acetyl derivatives.

The effect on 5-hydroxytryptamine release from rabbit platelets to plasma of ten known sympathomimetic or anorectic phenethylamines and eight N- or O-acetyl derivatives of these substances were studied in order to find possible structure-action relationships and a possible correlation to the pulmonary hypertension inducing ability of some anorexigens. Among the mainly indirectly acting sympathomimetics amphetamine and ephedrine showed a similar high 5HT-releasing effect. Tyramine was slightly weaker, while the direct acting phenylephrine (metaoxedrine) and orciprenaline were much weaker. Acetylation increased the 5HT releasing effect of amphetamine, ephedrine and tyramine but decreased this effect of phenylephrine and orciprenaline. Among the anorectic phenethylamines the 5HT-releasing effect decreased in the following order, aminorex, amphetamine, clophorex, chlorphentermine, diethylpropion (amphepramon), phentermine. With regard to aminorex, which is a releaser of platelet 5HT and an inhibitor of both MAO activity and 5HT uptake in pulmonary tissue, it seems possible that the pulmonary hypertension can be caused by high concentration of free 5HT.

Animals↗