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Biomedical subjects

M Mamelak

Publications and source records attributed to M Mamelak.

At least 37 records · Page 2Linked to original sources
PubMed1986

Treatment of narcolepsy with gamma-hydroxybutyrate. A review of clinical and sleep laboratory findings.

Previous studies on the effects of gamma-hydroxybutyrate (GHB) on the sleep and clinical response of patients with narcolepsy are reviewed. New information on 48 patients treated with GHB for as long as 9 years is presented. These studies indicate that 2.25 to 3.00 g of GHB, taken in conjunction with a low dose of a stimulant during the day, rapidly alleviate the symptoms of narcolepsy in most patients. Tolerance does not develop to this treatment regimen; neither have any patients discontinued the treatment because of side effects. In poor responders, daytime drowsiness and not cataplexy has been the most common residual symptom. Sleep studies reveal that GHB induces REM followed by slow wave sleep. Although total sleep time at night may be unchanged, sleep is less fragmented. GHB appears to be effective because it can induce the symptoms of narcolepsy and contain them at night. It is noteworthy, therefore, that the central biochemical changes induced by GHB also appear comparable to those found naturally in narcolepsy.

Female↗
PubMed1985

Brain adenylate cyclase activity in the amphetamine sensitized rat.

Behaviour was augmented in rats by treatment with 10 mg/kgm d-amphetamine twice a day for 10 days. A greater activation of adenylate cyclase was found in dopamine rich areas of these rats brains than in normal controls when the enzyme was tested with sodium fluoride and quanylimidodiphosphate. These results parallel similar findings in the brains of schizophrenics obtained at post mortem and support the use of amphetamine sensitization in rats as a model for schizophrenia.

Adenylyl Cyclases↗
PubMed1983

Effects of brotizolam on the sleep of chronic insomniacs.

Effects of 0.5 mg brotizolam on the sleep of chronic insomniacs were assessed electroencephalographically and subjectively over 14 days. Brotizolam (0.5 mg) increased total sleep time, decreased drowsy (stage 1) sleep and increased stage 2 sleep. At this dose it also decreased slow wave and rapid eye movement sleep. On withdrawal there was evidence of insomnia in some subjects during the first night. The drug was well tolerated. Further studies are indicated with lower doses of the drug.

Adult↗
PubMed1983

Effects of zopiclone on the sleep of chronic insomniacs.

The purpose of this study was to evaluate the short- and intermediate-term (21 days) effectiveness, as well as the carryover and withdrawal effects of 7.5 mg of zopiclone, a new short-acting hypnotic agent. 6 patients with chronic insomnia, ranging in age from 33 to 57, participated in the study. Both EEG sleep recordings and subjective rating scales were used to evaluate the drug. Zopiclone increased the total sleep time throughout its 3-week administration period although only during the short-term period was this increase statistically above baseline. There was no carryover effect nor rebound insomnia upon drug withdrawal. The drug significantly increased the duration of stage 2 sleep, decreased stages 3 and 4 sleep, and had no effect on the duration of REM sleep. There were no reported side effects.

Adult↗
PubMed1983

The effect of gammahydroxybutyrate on the H-reflex: pilot study.

Gammahydroxybutyrate (GHB) promotes cataplexy when given during the day, but decreases the incidence of daytime cataplexy when given at night. To understand the effects of GHB on this form of motor inhibition, we studied its actions on the H- and F-responses. The H-response is attenuated or abolished during cataplexy. GHB markedly inhibited the H-reflex response in normal and narcoleptic subjects, whether or not sleep was induced. It had no effect on the F-response. Prolonged motor inhibition at night by GHB may raise the threshold for inhibition during the day, accounting for the decrease in daytime cataplexy. The failure to affect the F-response suggests that GHB has a presynaptic site of action.

Adult↗
PubMed1982

Effects of zopiclone on the sleep of chronic insomniacs.

The purpose of this study was to evaluate the short- and intermediate-term (21 days) effectiveness, as well as the carryover and withdrawal effects of 7.5 mg of zopiclone, a new short-acting hypnotic agent. 6 patients with chronic insomnia, ranging in age from 33 to 57, participated in the study. Both EEG sleep recordings and subjective rating scales were used to evaluate the drug. Zopiclone increased the total sleep time throughout its 3-week administration period although only during the short-term period was this increase statistically above baseline. There was no carryover effect nor rebound insomnia upon drug withdrawal. The drug significantly increased the duration of stage 2 sleep, decreased stages 3 and 4 sleep, and had no effect on the duration of REM sleep. There were no reported side effects.

Adult↗
PubMed1980

Effects of nocturnal gamma-hydroxybutyrate on sleep/waking patterns in narcolepsy-cataplexy.

Continuous 48-hour polygraphic recordings of sleep/waking patterns were performed on 14 patients with narcolepsy-cataplexy before and after 7-10 days of treatment of their nocturnal sleep with gamma-hydroxybutyrate (GBH). GBH improved the quality of night sleep by increasing the amount of slow wave sleep, reducing stage I, increasing sleep efficiency (percentage of time in bed spent asleep), and reducing the number of periods of short sleep under 15 minutes. Also nighttime REM sleep was reduced in latency and became less fragmented. The daytime period contained less slow wave sleep and REM sleep, and fewer episodes of prolonged sleep. Patients experienced reduction or loss of daytime attacks of irresistible sleep, cataplectic attacks, and other auxiliary symptoms. Residual daytime drowsiness subsequently improved on low doses of methylphenidate. Tolerance did not develop and there were no serious toxic side-effects. Four of the patients had been refractory to previous combinations of antidepressants and high doses of stimulants.

Adult↗
PubMed1979

The treatment of narcolepsy-cataplexy with nocturnal gamma-hydroxybutyrate.

Sixteen patients with narcolepsy and cataplexy were treated with gamma-hydroxybutyrate (GHB) given at night and tailored to achieve as continuous a night's sleep as possible. The dosage usually consisted of 1.5-2.25 gm orally at bedtime and then one or two further 1.0-1.5 gm doses with awakenings during the night, and totaled about 50 mg/kg. Apart from one patient who took only the bedtime dose, the subjective quality of night sleep improved in all patients and the number of irresistible daytime attacks of sleep and cataplexy substantially diminished. Some residual daytime drowsiness remained and this usually responded well to low doses of methylphenidate. Improvement has been maintained for up to 20 months without the development of tolerance. Two patients experienced adverse side effects necessitating withdrawal of GHB treatment, but no serious toxic effects have occurred.

Adult↗
PubMed1979

Narcolepsy: a family study.

We obtained medical and psychological assessments and 48-hr polysomnographic recordings on five sisters, three of whom had narcolepsy. Of the three, two were identical twins. All three narcoleptic sisters cited emotional stress and environmental demands for sustained performance as the major factors which aggravated their symptoms, and corresponding to this, the illness followed a different life course in each of the three. Most striking were the differences between the twin sisters in clinical symptoms and polysomnographic signs. One sister suffered from all the symptoms of narcolepsy and her sleep recording showed the typical sleep onset REM periods of the disease. Her twin suffered only from excessive daytime drowsiness and her sleep recording was normal--at least by the usual criteria. The sleep of all three narcoleptic sisters, however, was significantly more fragmented than that of their normal siblings. Our data suggested that excessive sleep fragmentation was a basic feature of narcolepsy and that it betrayed a constitutional predisposition for sleep to dissociate into its components and to become distributed around the nycthemeron. This process could be aggravated by emotional stress and by environmental demands for sustained vigilance, and this in turn, created the differences in symptoms and signs between individuals with identical genetic predispositions.

Aged↗
PubMed1978

Evidence for involvement of microtubules in the action of vasopressin in toad urinary bladder. I. Functional studies on the effects of antimitotic agents on the response to vasopressin.

The antimitotic agents colchicine, podophyllotoxin, and vinblastine inhibit the action of vasopressin and cyclic AMP on osmotic water movement in the toad urinary bladder. The alkaloids have no effect on either basal or vasopressin-stimulated sodium transport or urea flux across the tissue. Inhibition of vasopressin-induced water movement is half-maximal at the following alkaloid concentrations: colchicine, 1.8 X 10(-6) M; podophyllotoxin, 5 X 10(-7)M; and vinblastine, 1 X 10(-7)M. The characteristics of the specificity, time-dependence and temperature-dependence of the inhibitory effect of colchicine are similar to the characteristics of the interaction of this drug with tubulin in vitro, and they differ from those of its effect on nucleoside transport. Inhibition of the vasopressin response by colchicine, podophyllotoxin, and vinblastine is not readily reversed. The findings support the view that the inhibition of vasopressin-induced water movement by the antimitotic agents is due to the interaction of these agents with tubulin and consequent interference with microtubule integrity and function. Taken together with the results of biochemical and morphological studies, the findings provide evidence that cytoplasmic microtubules play a critical role in the action of vasopressin on transcellular water movement in the toad bladder.

Animals↗
PubMed1978

An amphetamine model of manic depressive illness.

Many features of manic-depressive illness can be mimicked in man by the use and withdrawal of amphetamines. In higher doses these drugs induce a syndrome virtually indistinguishable from paranoid schizophrenia. In this paper, some of the biochemical and physiological effects of the amphetamines are examined with the hope of clarifying the nature of the biological changes in these two major functional psychoses. The actions of the amphetamines are shown to reveal the operation of specific homeostatic or adaptive nervous mechanisms. These appear likely also to operate in adaptation to psychological stress. Evidence is presented that these mechanisms are malfunctioning in manic-depressive and acute schizophrenic states and that this accounts for many of the clinical features of these conditions.

Adaptation, Psychological↗
PubMed1977

The effects of gamma-hydroxybutyrate on sleep.

Sodium gamma-hydroxybutyrate (GHB) is a remarkably safe and nontoxic hypnotic agent which is reported to be free of addicting properties. It is also a normal metabolite of the mammalian nervous system. We examined its effects on the sleep-EEG of eight patients with histories of impaired sleep, as a prelude to a more detailed study of its clinical potential. Sleep induced with GHB was indistinguishable subjectively from natural sleep as well as by behavioral and electroencephalographic criteria. Unlike most synthetic hypnotics, GHB increased delta sleep and did not suppress REM sleep. It shortened the REM sleep latency and shifted REM sleep into the first third of the night. On one occasion it induced a sleep onset REM period which was experienced as an attack of sleep paralysis. Withdrawal was simple; there was no REM sleep rebound and sleep patterns immediately returned to their pre-drug form. Its major clinical drawback was its short duration of action: its hypnotic effect lasting only 2 to 3 hr. We suggest that GHB may serve as the prototype for a new class of hypnotic compounds derived from natural sources and capable of activating the neurological mechanisms of normal human sleep.

Adult↗
PubMed1973

Vasopressin: possible role of microtubules and microfilaments in its action.

Colchicine, vinblastine, podophyllotoxin, and cytochalasin B inhibit the action of vasopressin and cyclic adenosine monophosphate on osmotic water movement across the toad bladder. The findings suggest that microtubules, and possibly microfilaments, play a role in the action of vasopressin, perhaps through involvement in the mechanism of release of secretory material from the bladder epithelial cells.

Animals↗
PubMedDate not supplied

A comparative 25-night sleep laboratory study on the effects of quazepam and triazolam on chronic insomniacs.

The short- and intermediate-term actions, as well as the carryover and withdrawal effects, of quazepam , a new benzodiazepine hypnotic with a half-life of 60 to 100 hours, were compared with those of triazolam, a triazolodiazepine hypnotic with a half-line of 2 to 3 hours. Both the subjective effects of these drugs as well as their objective actions on the sleep EEG were sought. The study was conducted on two groups of six subjects with chronic insomnia who ranged in age from 32 to 56 years. Each subject was studied for 25 consecutive nights. Placebo was administered at bedtime on the first four nights, followed by 30 mg quazepam or 0.5 mg triazolam on the next 14 nights and by placebo again on the ensuing seven withdrawal nights. Both drugs increased the total sleep time during their administration and improved the subjective quality of sleep. Major differences, however, were observed on withdrawal. A significant and marked decrease in the total sleep time occurred with triazolam on the first withdrawal night. With quazepam , rebound insomnia was not observed at any time during the seven-day withdrawal period.

Adult↗