Biomedical subjects
Publications and source records attributed to Z S Herman.
The new achievements in the understanding of acetylcholine (ACh) synthesis, storage, metabolism, the neuronal action, the structure of cholinergic synapses and the nature of cholinergic receptors in the central nervous system are described. Moreover, interactions of cholinergic mechanisms with adrenergic, serotoninergic, GABA-ergic and histaminergic systems in the brain are discussed.
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In patients with supratentorial tumours and posterior fossa tumours or in the third ventricle the concentrations of HVA and 5-HIAA were determined in the cerebrospinal fluid from the lateral ventricle. A significantly greater concentration of HVA and 5-HIAA was found in the patients with considerable hydrocephalus caused by occlusion of the third ventricle, aqueduct or fourth ventricle as compared with the cases of supratentorial tumours and with cases of moderate hydrocephalus and partial block of fluid outflow caused by third ventricle tumorous or posterior fossa tumours.
The levels of biogenic amines and their metabolites were determined in different parts of brain or cerebral-spinal fluid 0.5, 1, 6, 12 or 24 h after experimental cerebral concussion. Cerebral concussion in the rat leads within 6 h to an increase in 5-hydroxytryptamine and a decrease in dopamine utilization in the striatum. That imbalance between the functional state of serotoninergic and dopaminergic neurons may partly explain the development of vasospasms, ischemia and edema brought about by the brain mechanical trauma. Moreover, after cerebral concussion an evident decrease in NA level in discrete brain areas and a decreased DA release in the whole brain occur. In conclusion it is suggested that the alterations of catecholamine and 5-hydroxytryptamine utilization in discrete brain areas, especially in the striatum are the characteristic feature of disturbances after experimental brain concussion.
Choline acetyltransferase (Ach-T) and acetylcholinesterase (Ach-E) activities in mice brain during the reverse action by imipramine, pheniprazine and pargyline to the syndrome elicited by intraperitoneal administration of Ro 4--1284 were investigated. A single dose of imipramine did not reverse reserpine-like syndrome whereas inhibited Ach-E activity and increased Ach-T activity at the same time. The reversal of reserpine-like syndrome by administration of pargyline, pheniprazine or chronic administration of imipramine was accompanied by no changes in Ach-E and Ach-T activities.
Nine Met-enkephalin analogues containing D-alanyl residue in position 2 and/or 3-(2-naphthyl)-D-alanyl residue in positions 2 and 4 have been obtained. Their biological activity has been determined after intracerebroventricular administration to rats. Almost all compounds appeared strongly toxic causing the death of the animals. Only [D-2-Nal2,4, Met5-OMe]--enkephalin exerted an analgesic effect after the administration in the form of fine suspension.
In male R-3 mice alpha-endorphin (alpha-E) was injected intracerebroventricularly (icv, 10 ng) or intrathecally (ith, 1 or 10 ng). The antinociceptive activity (tail immersion test) and the locomotor activity (photocell actometers) were measured. alpha-E administered icv or ith induced an evident antinociceptive effect which was prevented by the previous naloxone injection. Locomotor activity was inhibited by icv but not ith administration of alpha-E. This effect was not changed by naloxone. The results show that exogenous alpha-E elicits different effects when applied icv or ith, and induces antinociceptive effect at the spinal level through opioid receptors.
This paper reviews data concerning the possible role of opioid neuropeptides in the central action of psychotropic drugs. The results summarized provide an evidence that the long term interruption of the central dopaminergic mechanisms by administration of neuroleptics causes specific alterations in the content, release and biosynthesis of several opioid peptides. Moreover, the dynamic changes of the enkephalin level in brain structures after one year of fluphenazine administration were described. The acute and chronic treatment with benzodiazepines induced pronounced changes in brain enkephalin concentrations. The first evidences are provided that chronic antidepressant treatment changes the level of enkephalins in discrete brain areas.
In rats and mice the basic pharmacological properties of tryptamide (TRP), a novel antiinflammatory substance were studied. The LD50 doses were for male rats 1260 mg/kg ip or 8.5 g/kg po, for male mice: 1980 mg/kg ip or 9.3 g/kg po. TRP produced evident antiinflammatory effects of potency comparable with those of phenylbutazone when studied by means of carrageenin-induced rat paw oedema and prostaglandin synthetase activity in vitro. TRP reversed pyrogen-induced hyperthermia in rats, elicited analgesic effects in rats, but not in mice, prolonged the time of hexobarbital sleep in rats and inhibited locomotor activity in rats and mice. TRP has not elicited side effects on the circulatory system of rats and cats. It is concluded that TRP may undergo clinical trials as a potential antiinflammatory drug. During these trials the attention should be paid to possible central side effects the drug.
In nine splenectomized male dogs a splenic artery, -splenic vein shunt was made. Before splenectomy and 3, 6 and 18 months after arterialization of portal blood, different metabolic and endocrine parameters were estimated. Long-term arterialization of portal blood was followed by only insignificant increase of portal vein pressure but a significant drop of pCO2 and increase of pO2 in portal blood was recorded. Simultaneously, a significant decrease of the erythrocyte count, hematocrit value, serum cholesterol and uric acid levels, and a shortening of the T1/2 of insulin and glucagon were found. In contrast, long-term arterialization of portal blood was followed by a significant increase of serum triglycerides, alpha2-globulins, plasma renin activity, cortisol, gastrin and 25-hydroxyvitamin D, and by slight carbohydrate intolerance. No morphological abnormalities in the liver and kidney tissue were found. Data presented in this paper suggest usefulness of a splenic artery-splenic vein shunt in the treatment of some metabolic disorders and of the failing hepatocytes.
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The influence of imipramine (IMI) or amitriptyline (AMI) on the level of immunoreactive leu-enkephalin (ir-LENK) in the striatum and hypothalamus was studied in rats. Each drug was given by drinking water once or over periods of 1, 3, 4 and 6 months. The ir-LENK in brain perfusates was measured after 3 or 9 month treatment with IMI. The results obtained indicate that during prolonged administration of IMI the central enkephalinergic system is dynamically changed. We have observed that chronic (but not acute) administration of IMI induced different effects on LENK level in the examined structures than changes caused by treatment with AMI.
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Leu-enkephalin (LENK) injected intracerebroventricularly (icv) in a dose of 50-400 micrograms to male Wistar rats inhibited their open field locomotor activity. This effect was antagonized by 1 microgram icv of ICI 174864 but not by naloxone (NAL). Doses of 5 and 10 micrograms of ICI 174864 icv induced a characteristic abnormal behavioral syndrome, which was inhibited by icv LENK, but not by morphine. ICI 174864 potentiated the analgesic effect of morphine, whereas NAL inhibited it. The results indicate that ICI 174864 is an antagonist of central delta-opioid receptors. The abnormal behavior induced by higher doses of ICI 174864 is suggested as an experimental model for studying the central delta-opioid receptors.
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Prostaglandins (PGs) E1, E2, F2alpha injected intracerebroventricularly (icv) in rats, potentiated chlorpromazine (CPZ) and pimozide (PI) catalepsy similarly. Cataleptogenic effect of haloperidol (HL) was potentiated specifically be PGE2. These phenomena were diminished by apomorphine (AP). Phenoxybenzamine (PB) diminished the potentiating effect of PGE2 and PGF2alpha on CPZ catalepsy, and strongly inhibited PGE2 the potentiating effect on HL and on PI catalepsy. Propranolol (PN) diminished the potentiating effect on HL and on PI catalepsy. Propranolol PN) diminished potentiating effect of PG on HL catalepsy and increased this effect of PGE1 on PI catalepsy. All examined PG induced catalepsy only when given in high doses (50 or 100 microgram icv). Cataleptogenic effect of PGE2 and PGF2 but not of PGE1, was evidently inhibited by AP. PGS inhibited AP stereotypy. The results suggest that the central dopaminergic receptors blockade is involved in the mechanism of potentiation of neuroleptic induced catalepsy by PGs, and that PGs are similar to neuroleptics in some aspects of central action.
Male Wistar rats were treated with imipramine hydrochloride (IMI) in a dose of 2 or 10 mg/kg/24 h in drinking water for 2 weeks, 1, 3 or 6 months. Two or 72 h after the final treatment forced swimming test was performed. It was shown that 2 h after the final dose of 10 mg/kg of IMI the immobility time was reduced following a period of 1-6 month treatment but not after 2 weeks of IMI administration. The dose of 2 mg/kg of IMI has not changed this type of behavior at any time after IMI treatment. After 24 h IMI (2 or 10 mg/kg) decreased the immobility of rats. This paper presents for the first time that also after long-term treatment with IMI the evident effect on the time of immobility in the rat forced swimming test occurs.