Inhibition by gamma-hydroxybutyrate of chlorpromazine-induced increase in homovanillic acid.
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1. gamma-Hydroxybutyrate and its lactone precursor, gamma-butyrolactone, when administered in anaesthetic doses block the increase in the cerebral concentration of homovanillic acid normally observed after administration of chlorpromazine or haloperidol.2. Other hypnotics such as glutethimide, urethane, chloralose, chloral hydrate and thiopentone do not have this ability even when administered in anaesthetic doses.3. The ability of gamma-hydroxybutyrate to block the neuroleptic-induced increase in cerebral homovanillic acid is not due to a reduction in body temperature since a similar effect is observed in rats treated under conditions (32 degrees C) in which body temperature remains normal.4. Possible mechanisms for this action of gamma-hydroxybutyrate are discussed. (+info)
Sleep and hypnotics: further experiments.
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Two experiments compatible with that used to investigate the effect of clinical doses (200 mg.) of amylobarbitone were set up to investigate the effects of clinical doses of chloral hydrate (800 mg.), dichloral phenazone (1,300 mg.), and Mandrax (methaqualone 250 mg. and diphenhydramine 25 mg.) over a period of one to two weeks.Four healthy male subjects were used in each experiment and received placebo or drug throughout a period of six to eight weeks when control records, drug records, and drug withdrawal records were obtained.Chloral hydrate was found to depress rapid eye movement (R.E.M.) sleep appreciably though less consistently than amylobarbitone. No withdrawal R.E.M. sleep rebound was found.Neither dichloralphenazone nor Mandrax was found consistently to depress R.E.M. sleep, though occasional nights when R.E.M. sleep was low occurred more often with Mandrax.In the light of other experiments it is postulated that there exists a "threshold" in the dose of a hypnotic, and that when this is exceeded the drug will produce R.E.M. reduction. Thus it may be possible to prescribe a drug which is clinically useful while avoiding withdrawal effects. (+info)
Effects of some drugs on the responses of the rat isolated, innervated urinary bladder to indirect electrical stimulation.
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1. The effects of some drugs known to inhibit transmission in the superior cervical ganglion and at the neuromuscular junction were investigated on the cholinergic nerve-smooth muscle junction, using the rat isolated innervated urinary bladder preparation.2. HC-3 and Win 4981 inhibited the indirectly evoked contractions; the block was typically slow in onset, depended on the rate of stimulation and was partially reversed by choline. The moderate coincident inhibition of acetylcholine-responses disappeared after washing the tissue, while the block of the neuronally evoked contractions persisted.3. Morphine, methylpentynol carbamate, chloral hydrate and strychnine inhibited indirectly evoked contractions without inhibiting the responses to acetylcholine. Paraldehyde inhibited both types of response.4. Hexamethonium, mecamylamine and tubocurarine had no effect on either type of response. Tetraethylammonium augmented both types of response; the augmentation due to lower concentration was followed by a moderate block of the neuronally evoked contractions.5. Small concentrations of procaine markedly inhibited responses to acetylcholine and produced a partial block of the neuronally evoked contractions.6. None of the drugs affected conduction in the isolated phrenic nerve.7. All the drugs other than paraldehyde and procaine appeared to act at the nerve terminals. The results are generally consistent with the view that HC-3 and Win 4981 act by limiting transport of choline across nerve membrane and that the other drugs act by inhibiting the release of acetylcholine. A reduction in sensitivity of the effector cell membrane may account, wholly or in part, for the action of paraldehyde and procaine. (+info)
The specific effect of potassium on transmitter release by motor nerve terminals and its inhibition by calcium.
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1. There exist two distinct effects of potassium on the transmitter release system, one which develops rapidly and another which becomes maximal much more slowly. The fast effect is inhibited by raised Ca(2+), which does not inhibit transmitter release evoked by depolarizing pulses. Thus the fast effect is not secondary to nerve terminal depolarization.2. The fast effect of K(+) was found to consist in an increase in the slope of the linear relation between log m.e.p.p. frequency and nerve terminal depolarization. This effect is complete within a few seconds, is inhibited by raised Ca(2+), and is not produced by prolonged focal or electrotonic depolarization, which instead tends to reduce the slope of log m.e.p.p. frequency vs. depolarization.3. A slope change effect like that of K(+) was not found with ouabain or ethanol, nor did these agents depress the slope change effect of K(+). The specific action of K(+) was not exerted on release evoked in the absence of Ca(2+) by ethanol, chloral hydrate, or raised osmotic pressure.4. It is suggested that the specific action of K(+) is to increase the lability of nerve terminal Ca permeability with respect to depolarization of the nerve terminal membrane, while the slow effect of K(+) simply reflects nerve terminal depolarization, slow to become maximal because of diffusion barriers limiting access of raised K(+) to the Ranvier nodes of motor axons. (+info)
Effects of some centrally acting drugs on acetylcholine synthesis by rat cerebral cortex slices.
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1. Brain cortex slices from rats injected i.p. with urethane (1 g/kg), chloral hydrate (350 mg/kg) or physostigmine (0.75 mg/kg) were examined for acetylcholine (ACh) content, cholinesterase (total enzyme) activity and formation of (14)C-ACh from carbon (14)-uniformly labelled glucose (U-(14)C-D-glucose) in the presence of 0.01 mM physostigmine.2. Slices from rats treated with urethane, chloral hydrate, or physostigmine contained significantly higher concentrations of ACh than slices from untreated animals.3. Only slices from physostigmine-treated rats had a significantly lower cholinesterase activity.4. Slices from urethane- or chloral hydrate-treated animals formed significantly less (14)C-ACh than slices from untreated or physostigmine-treated rats when incubated in 4 mM K(+) medium. In an ACh-releasing medium (31 mM K(+)) slices from rats treated with urethane or chloral hydrate and slices from untreated rats formed similar amounts of (14)C-ACh.5. Slices from rats treated with atropine (25 mg/kg) or pentylenetetrazol (75 mg/kg) had a similar ability to form (14)C-ACh as slices from untreated animals when incubated in either 4 or 31 mM K(+) medium.6. These findings suggest that the intraneuronal ACh concentration is a limiting factor in the regulation of ACh synthesis. (+info)
Hyperactivity: a lead-induced behavior disorder.
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Mice were exposed to lead from birth by substituting solutions of lead acetate for the drinking water of their mothers. The suckling mice were thus exposed to lead through their mother's milk and, at weaning, directly through the drinking water. Controls received equal concentrations of sodium acetate. No deaths of offspring or mothers occurred during the first 90 days of exposure. It has been suggested recently that lead exposure may account for some incidences of behavior disorders in children. Levels of motor activity of individual offspring were measured from weaning until 70 days of age in specially designed activity cages. Lead-treated mice were more than three times as active as age-matched or size-matched controls. Treated and control animals were administered drugs currently used in the treatment and diagnosis of hyperactivity in children. All control animals responded as expected to all drugs used in this study. However, lead-treated mice responded paradoxically to d- and l-amphetamine, methylphenidate, and phenobarbital. That is, the CNS stimulants suppressed their hyperactivity while phenobarbital exacerbated the lead-induced hyperactivity. These findings suggest that lead produces an animal model of hyperactivity which may have clinical relevance and which may explain some cases of hyperactivity in children. (+info)
A comparative study of three hypnotics: methyprylon, glutethimide and chloral hydrate.
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A controlled study designed to evaluate the hypnotic potentiality of methyprylon (300 mg.), glutethimide (500 mg.) and chloral hydrate (1000 mg.) was carried out on 50 in-patients experiencing long-standing insomina. The patients ranged in age from 21 to 60 years, the sexes were equally represented and the clinical diagnoses were psychoneurosis, reactive depression, or anxiety reaction. An interesting feature of the experimental design allowed for the exclusion of placebo reactors before the initiation of the main trials. No difference in effectiveness of maintaining sleep could be established among the three hypnotic agents, indicating that at the usual levels of statistical significance, all three agents were equally effective as hypnotics. However, a significant trend (P = .05) was found for methyprylon (Noludar) to be the most effective and chloral hydrate to be the least effective of the three drugs in maintaining sleep. Methyprylon was found statistically (P = .05) to be the fastest sleep-inducing agent, whereas glutethimide (Doriden) proved to be the slowest of the three hypnotics with respect to sleep induction time. (+info)
Differential media for the identification of Bacillus anthracis.
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Knisely, Ralph F. (U.S. Army Biological Laboratories, Fort Detrick, Frederick, Md.). Differential media for the identification of Bacillus anthracis. J. Bacteriol. 90:1778-1783. 1965.-Two new differential media for the identification of Bacillus anthracis are described. Phenethyl alcohol and chloral hydrate were used as selective ingredients. These media should aid in the differentiation of B. anthracis from B. cereus and, if used in conjunction with other differential tests, they should also differentiate B. anthracis from the majority of other aerobic sporeforming bacilli. These media might also be useful in the classification of Bacillus species. (+info)