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Biomedical subjects

N Montanaro

Publications and source records attributed to N Montanaro.

At least 55 records · Page 3Linked to original sources

Phenytoin-induced increase in growth hormone response to levodopa in adult males.

Growth hormone and prolactin response to levodopa were evaluated before and after long-term phenytoin treatment in five men with previously untreated partial epilepsy. After phenytoin treatment, growth hormone response to levodopa increased. There was a close relationship between growth hormone response to levodopa and plasma phenytoin concentrations. These findings suggest a phenytoin-induced dopaminergic activity at the hypothalamic-pituitary level in adult males.

Adult↗

Time course of rat motility response to apomorphine: a simple model for studying preferential blockade of brain dopamine receptors mediating sedation.

The present work proposes a simple behavioral method for studying the ability of certain neuroleptics to block preferentially dopamine receptors subserving sedation. The model is based on the temporally biphasic motor response induced in rats by a single critical dose of apomorphine. It was chosen from a preliminary apomorphine dose-response study which showed that the same doses between 6.25 and 625 micrograms/kg affected rat motility differently according to whether the animals were "naive" or "familiarized" to the apparatus for 90 min before administering the drug. When the motility response of naive rats to 300 micrograms/kg of apomorphine was recorded immediately after SC injection, an initial (1--5 min) inhibition and a subsequent (20--45 min) stimulation of motility were obtained. (--)-Sulpiride (1.25--50 mg/kg) was found to be approximately 6-fold more effective in counteracting the apomorphine inhibition than stimulation of locomotion. Haloperidol (0.005--0.1 mg/kg) incompletely antagonized apomorphine inhibition and markedly blocked stimulation, which suggests that it has no preferential activity on dopamine receptors subserving sedation. The results were in accordance with those obtained by other authors with different paradigms, and indicated that the time course of the rat motility response to a single dose of apomorphine may constitute a useful model for detecting selective influences on different dopamine receptors.

Animals↗

Phenobarbital and propranolol in essential tremor: a double-blind controlled clinical trial.

In a double-blind study with Latin square design, phenobarbital (about 1.3 mg per kilogram), propranolol (about 1.7 mg per kilogram), and placebo were given orally for 1 month to 12 patients with essential tremor. By clinical evaluation, only propranolol appeared to be significantly more effective than placebo. As judged by tests of manual skill, none of the treatments significantly improved tremor. Patients' subjective evaluation and tremor amplitude measurement (by accelerometer) showed a significantly better effect of both propranolol and phenobarbital than placebo. These data suggest that phenobarbital may be a valuable alternative to propranolol in essential tremor.

Adolescent↗

Differential enhancement of behavioral sensitivity to apomorphine following chronic treatment of rats with (-)-sulpiride and haloperidol.

Rat exploratory activity as well as apomorphine-induced hypermotility and stereotyped behavior were assayed following acute (60 min before) or chronic (21 days) administration of sulpiride stereoisomers and haloperidol. Parallel groups of rats were assayed for their hypermotility and stereotyped responses to challenging doses of apomorphine 7 and 21 days after discontinuation of chronic treatments. Following its acute administration, (-)-sulpiride fully antagonized apomorphine-induced hypermotility without affecting the level of animal spontaneous activity and partially counteracted stereotyped behavior. Haloperidol completely suppressed both apomorphine responses and also depressed exploratory activity. Some tolerance to the anti-apomorphine effect of (-)-sulpiride groups exhibited enhanced behavioral sensitivity to apomorphine only with respect to hypermotility, whereas haloperidol groups were supersensitive with respect to both hypermotility and stereotyped responses. The results are discussed in terms of differential dopamine receptor supersensitivity arising from prolonged administration of butyrophenone and substituted benzamide.

Animals↗

Dialysable and non-dialysable hydroxyproline in the rat's urine: age related and diurnal variations.

1. Urinary dialysable and non-dialysable hydroxyproline, which are considered good indices of bone resorption and neoformation respectively, were determined in rats under conditions that modify skeleton metabolism, such as body growth and parathyroid or calcitonin administration. It was also investigated whether dialysable and non-dialysable hydroxyproline excretions showed significant circadian fluctuations in rats of different ages.2. Dialysable hydroxyproline excretion sharply decreased from the first to the fifth months of age and underwent further gradual reduction up to the fourteenth month of life. Non-dialysable hydroxyproline excretion followed a smoother decrease up to the fifth month, then remained constant. Urinary excretion of non-dialysable hydroxyproline expressed as a percentage of the total hydroxyprolinuria (n.d.%) slowly increased with advancing rat age.3. In 2-, 4- and 6-month old rats, dialysable hydroxyproline excretion showed significant circadian fluctuations with minima and maxima at the end of the dark and light fraction of the cycle respectively. Daily fluctuations were greater in young and adult rats (50-65% of the respective average levels) than in 4-month old rats (25%). Non-dialysable hydroxyproline excretion followed similar but less pronounced patterns. Significant circadian fluctuations of n.d.% were detectable only in 2- and 4-month old rats, with peaks at 04.00-05.00 hr, thus indicating that the bone formation/resorption ratio increased in the nocturnal fraction of the cycle.4. Young rats administered with calcitonin exhibited reduced levels of urinary dialysable but not of non-dialysable hydroxyproline when the hormone was given at 13.30 hr. No changes were observed when calcitonin was injected at 19.30 hr. On the contrary, both diurnal and nocturnal parathyroid hormone administration to young rats caused increased levels of dialysable and non-dialysable hydroxyproline of the same magnitude.

Age Factors↗

Behavioral supersensitivity to methamphetamine following chronic treatment with (--)-sulpiride in the rat.

Hyperactivity induced by methamphetamine (4 mg/kg i.p.) was actographically evaluated in rats chronically treated with sulpiride stereoisomers and haloperidol. The trial was repeated with half dose of the stimulant after 8 days of neuroleptic withdrawal. (--)-Sulpiride and haloperidol antagonized the response to the full dose of methamphetamine and induced behavioral supersensitivity to the challenging dose. (+)-Sulpiride strongly enhanced the effect of 4 mg/kg of methamphetamine, but no relevant changes in dopaminergic sensitivity followed.

Animals↗

[Diphasic action of apomorphine on motility of the rat. I. Dose-effect relationship in exploratory and basal motility].

The effect of 8 doses of apomorphine HCl (0 - 6.25 - 13.46 - 29.01 - 62.5 - 134.65 - 290.1 - 625.0 microgram/kg, s.c. 15 min before) upon rat 30-min locomotor activity was evaluated in naive animals and in rats habituated to the actometer for 90 min. The doses of 29.01 - 62.5 - 134.65 significantly inhibited the exploratory activity of naive rats and the higher doses did not significantly influence such elevated baseline motility. On the contrary, low baseline motility of habituated rats resulted unaffected by the lower doses of apomorphine, whereas it was greatly stimulated by the doses of 290.1 and 625.0. It was concluded that suitable baselines of rat motility are required for the appearance of apomorphine stimulating effects at pre- and post-synaptic dopamine receptor levels.

Animals↗

[Diphasic action of apomorphine on motility in the rat. II. Time aspects of the effect of a single dose].

The locomotor activity of rats subcutaneously treated with apomorphine HCl (300 microgram/kg, 30 sec before emmission into actometers) was evaluated every 60 sec for 1 hour. An inhibitory phase appeared in the first 6 min of recording in comparison to the more elevated values of the control group. From 18th to 44th min a more sustained activity was easily recognizable in treated rats in comparison to the decline of control values. The results were discussed by supposing that the first amounts of drug entering CNS stimulated pre-synaptic dopamine receptors and the full dose activated post-synaptic dopamine neurons. The study of time-course of a single dose of apomorphine could be a useful model for evaluating pre- and post-synaptic effects of antidopaminergic drugs.

Animals↗

Reduction of ECS-induced retrograde amnesia of passive avoidance conditioning after 5,7-dihydroxytryptamine median raphe nucleus lesion in the rat.

5,7-Dihydroxytryptamine (5,7-DHT), median raphe nucleus (MRN)-lesioned and sham-lesioned rats were submitted to one-trial passive avoidance conditioning followed by electroconvulsive shock (ECS) or sham-ECS. On test session (24 h later) MRN-lesioned rats presented a longer conditioned response and, chiefly, a remarkable reduction of ECS-induced retrograde amnesia in comparison to sham-lesioned animals. This effect appeared unrelated to major changes in spontaneous behavior: on training session MRN-lesioned rats exhibited a faster stepping-down from the platform; their exploratory activity into a novel cage was characterized by a slightly higher initial response; moreover MRN lesion did not significantly effect pain threshold. A reduced brain 5-HT functional activity following MRN lesion was suggested by the study of the hyperactivity syndrome induced by tranylcypromine plus L-tryptophan. Lastly, MRN-lesioned rats showed a significantly lower brain 5-HT steady level without differing from the sham-lesioned ones with respect to turnover rate. The reduction of ECS-induced retrograde amnesia observed in 5,7-DHT, MRN-lesioned rats was considered as due to a lower synaptic availability of 5-HT at the time of ECS administration.

5,7-Dihydroxytryptamine↗

Effect of intraventricularly injected ricin on protein synthesis in rat brain.

Ricin, a protein from the seeds of Ricinus communis which inhibits protein synthesis by eukaryotic ribosomes, is highly toxic when injected intraventricularly to rats, the LD50 being 0.241 micrograms/rat at 72 hr and 0.084 micrograms/rat at 7 days. Poisoned animals showed signs of central depression; they did not die before 20 hr of intoxication. Incorporation of amino acids in vivo into brain total protein and into brain ribosomes was impaired, as was protein synthesis in vitro by microsomes isolated from the brain of poisoned rats.

Animals↗

Bromolysergide and methysergide protection against ECS-induced retrograde amnesia.

Bromolysergide (BOL 148) and methysergide (UML 491), 2 mg/kg intraperitoneally, and saline were administered to rats 45 min before one-trial passive-avoidance conditioning followed by electroconvulsive shock (ECS) or sham-ECS (ECS). On test session (24 h later), the groups treated with both BOL 148 and UML 491 exhibited a clear-cut retention in comparison to saline-ECS rats. On the other hand, all drugged groups, regardless of their submission to ECS, showed a little less pronounced consolidation than saline-ECS rats. The antiamnestic effect brought about by the two drugs was discussed in terms of receptor antagonism against ECS-released brain serotonin, whereas the lower passive-avoidance level observed in treated animals was considered in relation to a possible antipunishment effect of antiserotoninergic treatment.

Amnesia↗

Effect of alpha-amanitin on brain RNA and protein synthesis and on retention of avoidance conditioning.

The effect of a sublethal dose of alpha-amanitin given intraventricularly to rats on retention of passive and active avoidance conditioning has been studied, together with the effect on brain RNA and protein synthesis in vivo. The toxin brings about a significant impairment of retention of both passive and active conditioning in rats poisoned 6 hr or 24 before training. Brain RNA synthesis is decreased at 6 hr after poisoning, whilst protein synthesis decreases at a later stage (not before 12 hr after poisoning). Thus in rats poisoned with alpha-amanitin memory consolidation is impaired when RNA synthesis is decreased, and before protein synthesis is affected.

Amanitins↗

Nonsteroidal antiinflammatory agents. 2. Synthesis and biological activity of 2-chloroindolecarboxylic acids.

The Vilsmeier and the Arndt-Eistert reactions have been employed for the synthesis of 1-phenyl-2-chloroindole-3-acetic acid (4). The antiinflammatory activity of 2-chloroindole-3-carboxylic acid (1), 1- methyl-2-chloroindole-3-carboxylic acid (2), 1-phenyl-2-chloroindole-3-carboxylic acid (3), and 4 was compared with the activity of indomethacin in the carrageenin rat edema. The best results are given by compounds 1 and 2 bearing H or CH3 at position 1 and COOH at position 3.

Animals↗

Double-blind cross-over clinical comparison of two 2'-chloro benzodiazepines: 7-chloro-5-(2-chlorophenyl)-1,3-dihydro-2H-1,4-benzodiazepin-2-one (chlordesmethyldiazepam) versus 7-chloro-5-(o-chlorophenyl)-1,3-dihydro-3-hydroxy-2H-1,4-benzodiazepin-2-one (lorazepam) in neurotic anxiety.

A group of 20 female neurotic inpatients has been treated with 7-chloro-5-(2-chlorophenyl)-1,3-dihydro-2H-1,4-benzodiazepin-2-one-(chlordesmethyldiazepan)- 7-chloro-5(o-chlorophenyl)-1,3-dihydro-3-hydroxy-2H-1,4-benzodiazepin-2-one (lorazepam) according to a double-blind cross-over design. For each drug clinical evaluations were performed by means of Hamilton's rating scale for anxiety states and of Overall and Gorham's brief psychiatric rating scale, at the beginning, after the first week and at the end of the two-week period of treatment, in opposite sequence. A statistically greater efficacy of chlordesmethyldiazepam in comparison to lorazepam was observed. Results are discussed with regard to benzodiazepine structure-activity relationships.

Adult↗

Single-blind evaluation of hypnotic activity of chlordesmethyldiazepam in No-placebo-reactor medical patients.

69 patients hospitalized for chronic respiratory diseases and complaining of moderate to severe insomnia were treated with placebo for 2 days, 36 subjects (52.17%) were discarded for their placebo responsiveness. To the remaining patients who suffered from severe insomnia, 7-chloro-5-(2-chlorophenyl)-1,3-dihydro-2H-1,4-benzodiazepin-2-one (chlordesmethyldiazepam, 2 mg orally) was administered for 7 consecutive evenings. The onset, duration, quality of sleep and the state on awakening were scored on the basis of patient subjective measurements. High scores of the four considered parameters were obtained during chlordesmethyldiazepam administration. Three treated patients complained of diurnal drowsiness. Results are discussed with regard to methodological problems in the evaluation of hypnotics.

Clinical Trials as Topic↗