Dyskinesia induced by long-term treatment with antipsychotic drugs: involvement of pre- and postsynaptic dopaminergic mechanisms.
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Biomedical subjects
Publications and source records attributed to J Engel.
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With the aid of spectroscopical methods the structure of (+)-(R)-alpha-[(S)-1-[(3,3-di-3-thienylallyl)amino]-ethyl]-benzyl-alcohol (tinofedrine, 1), a new cerebrally active compound, was confirmed. The relative and absolute configuration is discussed in view of spectroscopic data.
The synthesis of [R-(R*,S*)]-7-[2-[(2-hydroxy-1-methyl-2-phenylethyl)amino]-ethyl]-3,7-dihydro-1 ,2-dimethyl-1H-purine-2,6-dione (Cafedrine) and its stereoisomers is reported. By means of 1H- and 13C-nmr spectroscopy the relative configuration of the two asymmetric centres is ascertained and the absolute configuration is discussed. The EI-mass spectrometric fragmentation of cafedrine has been elucidated.
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Spontaneous perforation of the colon by a barium stereoraceous fecaloma occurred two weeks after an upper gastrointestinal x-ray without intervening constipation or symptoms of intestinal obstruction. This patient is chronically uremic as have been a high percentage of the few previously reported similar cases. Renal failure and the associated factors in the management of uremia such as antacids, barium examinations, inactivity, changes in diet and finally abnormalities of the colonic mucosa due to uremia may all predispose these patients to an increased risk for this unusual serious complication.
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Ninety females underwent mastectomy for breast cancer and were thereafter investigated to determine whether nerve entrapments were responsible for some of the disabling symptoms in their arms. The majority of these patients suffered from fullness (edema), numbness, paraesthesia, weakness and pain of the arm on the mastecotmized side. Lymphedema of varying degrees found in 50% of these patients was associated with brachial plexus entrapment and carpal tunnel syndrome (CTS). 28% of the patients has CTS, and 28% suffered from brachial plexus entrapment of the arm on the mastecotmized side, as compared with 8% and 5%, respectively, on the nonoperated side. 12% of the patients suffered from both types of entrapment. Thus we consider that brachial plexus entrapment and carpal tunnel syndrome should be added to the list of complications following mastectomy, with lymphedema playing an active part in their development.
The distribution of the Epinephrine forming enzyme (PNMT) activity and Epinephrine (E) levels was investigated in the medulla oblongata of spontaneous hypertensive rats (SH-rats) and in two normotensive strains, namely Wistar Kyoto rats (WK-rats) and Wistar rats. The PNMT activity increases progressively from the caudal to rostral parts in the C1 and C2 regions of the medulla oblongata. The enzyme activity and the E levels are in all parts of the C1 and C2 regions higher in Wistar rats than in WK-rats. The PNMT activity in all parts of the C2 region (with the exception of the caudal region), and in the middle part of the C1 region is higher in SH-rats than in WK-rats. The E levels in the SH-rats are higher than in WK-rats in the mediocaudal parts of the C2 and C1 regions.
The effect of gamma-butyrolactone (GBL) on the accumulation of dopa after inhibition of aromatic amino acid decarboxylase was studied in rats following chronic treatment with ethanol. The GBL-induced dopa accumulation was significantly decreased in ethanol-treated rats. With the increased duration of the ethanol treatment this effect appears to be more marked in the limbic forebrain. It is suggested that chronic ethanol treatment may produce a decreased sensitivity of central GABA receptors.
Ketamine in a dose of 100 mg/kg (IP) produced stereotypic behavior and vigorous rotation in adult male Sprague-Dawley rats. The first rotation phase, accompanied by head swinging, was short and terminated by the anesthetic phase which lasted 20-30 min. The second rotation phase began 1-3 min after the end of the anesthetic phase. A single dose of GABA-T inhibitors, gamma-vinyl GABA (1200 mg/kg, IP) or gamma-acetylenic GABA (100 mg/kg, IP) administered 4 hours prior to ketamine, shortened the first rotation phase, increased the anesthetic phase, changed the pattern of postanesthetic rotation and reduced total and net rotation scores. Picrotoxin (3 mg/kg) given 10 min prior to ketamine tended to act in the opposite direction although none of its effects reached statistical significance.
Pretreatment of adult male Sprague-Dawley rats with a single dose of gamma-vinyl GABA (GVG) (1200 mg/kg, IP) or gamma-acetylenic GABA (GAG) (100 mg/kg, IP) did not affect the threshold of metrazol-activated generalized seizures, but increased their duration to the point of status epilepticus. In rats with epilepsy kindled by amygdaloid stimulation, a single dose of GVG (800 mg/kg, IP) and five subsequent daily administrations of GAG (80 mg/kg, IP) tended to reduce the motor manifestations of seizures leaving unaffected their electrographic pattern. The effects of GVG and GAG are attributed in part to decreased arousal. Practical implications of these findings are discussed.
The synthesis of catecholamines and serotonin in the brains of castrated male rats was analyzed at either various times after castration or at various ages. It was found that (a) castration of rats at 50 days or later causes an increase in brain monoamine synthesis, and (b) this phenomenon was not observed until 20 days after castration. The increase in brain monoamine synthesis following castration was counteracted by treatment with testosterone, thus relating the biochemical consequences of castration with changed hormonal conditions of the animal. It is suggested that testosterone exerts an inhibitory influence on monoamine synthesis.
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