[EFFECT OF MEDIATOR-TYPE DRUGS ON HUMAN PSYCHOPHYSIOLOGICAL STATUS DURING MODEL OPERATOR ACTIVITY].

In a placebo-controlled study, changes in psychophysiological status of operators (38 healthy male volunteers aged 23-35 years) performing 4-hour model operator activity were evaluated after a single oral administration of typical representatives of the different classes of drugs (haloperidol, proroxan, yohimbine hydrochloride, propranolol, mesocarb, isoprenaline, Belladonna extract, anabasine hydrochloride, valproate sodium, and phenazepam), which are used for the treatment, rehabilitation and prophylaxis of common diseases. It was found that all the drugs modified to a greater or lesser extent some components of the model operator activity. Isoprenaline and phenazepam had the most negative effect on the psychophysiological indicators and quality of the modeled operator activity. The results should be considered before administration of such drugs to working operators.

Comparison of the inhibitory efficacy of four belladonna drugs on gastrointestinal movement and cognitive function in food-deprived mice.

Belladonna drugs, scopolamine (Sco), atropine (Atr), anisodine (AT(3)), and anisodamine (Ani), frequently used for gastrointestinal motility disorders often produce adverse effects on the central nervous system. In the present work, these drugs (0.05, 0.5, 5, and 50 micromol kg(-1), i.p.) were evaluated for their potential to inhibit gastrointestinal motility and cognition in mice. Results showed that the maximum inhibitory rates of Sco, Atr, AT(3), and Ani on gastric emptying and small intestinal movement were 29.78, 40.69, 12.30, and 17.99% and 51.98, 58.46, 46.51, and 46.22%, respectively. The affinities of Sco, Atr, AT(3), and Ani for muscarinic receptors in the whole mice were 1.62, 1.48, 2.28, and 1.11 micromol kg(-1) for the stomach or 0.30, 1.12, 0.59, and 1.14 micromol kg(-1) for the small intestine, respectively. The minimal effective doses for impairing avoidance-response learning were 5 micromol kg(-1) for Sco, Atr, or AT(3) and 50 micromol kg(-1) for Ani. The initial doses for insulting the avoidance-response memory or open-field memory were 0.5, 5, 5, and 50 micromol kg(-1) or 5, 5, 5, and >50 micromol kg(-1) for Sco, Atr, AT(3), and Ani, respectively. We conclude that the relative susceptibility of the mouse's tissue or function capacities towards the inhibitory effects of belladonna drugs is small intestine > stomach > avoidance-response memory > avoidance-response learning > open-field memory.

Neurotropic, immunological and gastric effects of low doses of Atropa belladonna L., Gelsemium sempervirens L. and Poumon histamine in stressed mice.

Previous studies realized in the laboratory have indicated that application of experimental stress (such as unavoidable footshock) induced significant behavioral, gastric and immunological alterations in mice. The aim of this study was to evaluate effects of low doses of Atropa belladonna L., Gelsemium sempervirens L. and Poumon histamine on stress-induced behavioral, immunological and gastric alterations. Locomotor, postural and exploratory activities have been evaluated by two behavioral tests: light/dark box and staircase tests. Immunological studies were investigated to count white blood cells subpopulations (lymphocytes, neutrophils, monocytes and basophils) by coulter counter. The severity of gastric erosions was evaluated by microscopic technique in mice after experimental stress. The results have demonstrated that low doses of G. sempervirens L. and A. belladonna L. had a significant neurotropic and protective effects on behavioral and gastric alterations induced by experimental stress. The immunological protective effects observed were probably induced via their neurotropic effects. The P. histamine showed a significant immunoprotective and gastroprotective effect in mice exposed to experimental stress.

Belladonna alkaloids-induced behavioral changes and amnesia on open-field and step-through in 18-, 28-, and 38-day-old mice.

AIM: To study the age-related changes of atropine (Atr), scopolamine (Sco), anisodine (AT3), and anisodamine (Ani) on behaviors and memories. METHODS: The behaviors and memories were measured with open-field test and step-through task. M-cholinergic receptors were determined by [3H] quinuclidinyl benzilate ([3H] QNB). RESULTS: During acquisition session (d 1) the 18-, 28-, and 38-d-old mice pretreated with Atr, Sco, and AT3 (0.02, 0.2, 2, or 20 mg.kg-1, i.p.) in open-field test showed increase in walking counts by 26%-42%, but decrease in rearing, grooming, and defecating counts for 50%-92%, 67%-100%, and 75%-100%, respectively. On recall session (d 2) the walking and rearing behaviors in the 18- and 28-d-old mice receiving Atr, Sco, and AT3 on d 1 were higher than those in the mice receiving saline. But a lower grooming behavior on d 2 was found in the mice receiving the drugs on d 1. On d 1 Ani 20 mg.kg-1 reduced the rearing behavior by 50% in 18-d-old mice and defecation by 33%-36% in 18- and 28-d-old mice. All the 4 belladonna alkaloids increased the number of avoidance-response errors and decreased the retention latencies in step-through task. Bmax of [3H] QNB binding sites in frontal cortex and hippocampus regions in the 38-d-old mice increased 7% and 23% vs in the mice of 18 d of age, respectively. CONCLUSION: 1) The effects of the belladonna alkaloids on behaviors and memories in adult mice were weaker than those in young mice. 2) The belladonna alkaloids-induced amnesia on passive avoidance-response in step-through was more sensitive than behavioral changes and amnesia on open-field. 3) According to the lowest effective doses which insulted the behaviors or memories in young mice, Sco was about 10, 100, and 1000 times more potent than Atr, AT3, and Ani, respectively.

Does a highly diluted homoeopathic drug act as a placebo in healthy volunteers? Experimental study of Belladonna 30C in double-blind crossover design--a pilot study.

A basic tenet of homoeopathy is that remedies which do not contain active molecules can have effects on the healthy human organism, by virtue of the specific preparation process of stepwise dilution and succussion, called potentization. The claim that a so called high 'potency' of a homoepathic remedy, Belladonna C30, could produce effects different from placebo, was investigated in a pilot study. In a double-blind crossover trial, 4 weeks of Belladonna C30 were compared to 4 weeks of placebo in 47 healthy volunteers. Data were collected daily. The number and types of changes were recorded into a predefined category system. Single-case evaluation showed differences between the two experimental phases for 21 subjects. Group evaluation showed no clearcut differences. The claim that homoeopathic potencies can produce symptoms other than placebo in healthy subjects should be put to further scrutiny.

[Evaluation of the activity on the mouse CNS of several plant extracts and a combination of them]. / Valutazione dell'attività sul S.N.C. del topo di alcuni estratti vegetali e di una loro associazione.

Some activities of seven vegetable extracts and an association of them given by oral route were tested on the C.N.S. of the mouse. Among these, Crataegus oxyacantha and, less clearly, Valeriana officinalis show some sedative activity, whereas the extract from Passiflora incarnata gives some anxiolytic effect. Matricaria chamomilla and Piscidia erythrina stand in an intermediate position between the previous ones. Hyoscyamus niger proved to be active in only one of the tests performed, whereas Atropa belladonna did not show any activity on the C.N.S. The association of the seven extracts seemed to act in a synergetic way, the resulting activity being sedative at high dosage and anxiolytic at low dosage.

Sedation for dental treatment of infants. I. Physiology and pharmacology.

The principal functions of the central nervous system, the pharmacology, and the effect on the central nervous system, of a number of drugs used for a sedation technique for young children are described. This information is presented as a foundation for the application of clinical procedures.

Some factors influencing the neurotoxicity of intrastriatal injections of kainic acid.

Intrastriatal injections of kainic acid are known to destroy striatal neurons including many containing choline acetyltransferase (CAT) and glutamic acid decarboxylase (GAD). Using these enzymes as indices of neuronal loss, the neurotoxicity of small doses of kainic acid was found to be influenced by injection time and volume. It was partly blocked by coinjection of some but not all glutamate antagonists or by prior lesioning of the corticostriatal tract. Other adjuvants, drugs, or lesions tested had little modifying effect, except that changes in the dopaminergic system seemed to increase the toxicity towards cholinergic but not GABAnergic systems. High-affinity glutamate accumulation by neostriatal synaptosomes was significantly increased 1--7 days following kainic acid injections. MAO and acetylcholinesterase activities were depressed in kainic acid-lesioned striata but not nearly as much as were CAT and GAD. An indirect mechanism involving glutamate release and inhibition of reuptake is suggested for kainic acid neurotoxicity.

Uropharmacology: part VI. Parasympathetic depressants.

A discussion of the various parasympathetic depressants is presented. Belladonna alkaloids include atropine, the prototype, and scopolamine. Synthetic drugs include quaternary ammonium compounds with antimuscarinic activity such as methantheline, propantheline, and other drugs such as isopropamide, pipenzolate methylbromide, and diphemanil methylsulfate. A miscellaneous class of drugs such as hemicholinium, valethamate, and oxybutynin chloride also possesses parasympathetic depressant activity. The pharmacologic properties and clinical usage of these drugs are discussed.

Effect of antidiarrheal and antimotility drugs on ileal excreta.

Commonly used antimotility and antidiarrheal drugs were administered to six ileostomized subjects to determine whether their normal ileal excreta and that induced by prune juice could be altered. A total of 49 studies were performed, 21 with and 28 without prune juice. Bismuth subgallate was the only drug which significantly reduced the normal ileal excreta (P less than 0.05). Codeine sulfate decreased the ileal excreta in two of three subjects in either type of study. The third subject was a nonresponder to drugs. Deodorized tincture of opium (DTO) and diphenoxylate (Lomotil) were also effective in some subjects. Propantheline, tincture of belladonna, Sorboquel, and Kaopectate did not appear to decrease ileal excreta. Calcium carbonate, on the other hand, increased ileal excreta; fat excretion was also increased.

Comparative study of the effect of atropine, P2AM, and Buscopan. Total belladonna and hyoscyamus alkaloids on parathion poisoning.

Among the available antidotes used against parathion poisoning, atropine and Buscopan are tolerated in relatively high doses by rats. Hyoscine (in very small doses), T. Bel. Alk. and T. Hyosc. Alk. (better results in small doses, also for dogs), P2AM (of superior antimuscarine action) are redommended with each of the preceding drugs than either alone or in combination with Buscopan.

Physiologic/clinical comparisons of a sustained-release decongestant combination, its components and placebo in patients with allergic rhinitis.

Fifteen subjects with chronic allergic rhinitis had measurements of nasal airways flow/resistance (Rn) made before, and for 12 hours after, single doses of a sustained release decongestant combination, some of its components given alone or together, and placebo, in a randomized double-blind trial. The magnitude of improvement in Rn was statistically greater for the the four active preparations than for placebo over the first 8 hours; the effects of phenylpropanolamine/chlorpheniramine were still present after 10 hours, while at the end of 12 hours only the full triple-drug capsule had significant activity. Patient-estimates of symptomatic improvement generally mirrored these physiologic changes although statistical differences among the active capsules were not delineated. The data confirm the ability of electronic posterior rhinometry to discriminate between the effects of active medications and placebo at the 95 per cent confidence level or better and suggest that observed decreases in elevated Rn mean reflected helpful clinical activity as well as increased nasal patency.