[Hypotensive and miotic action of stabilized solutions of physostigmine and physostigmine-pilocarpine (experimental data)].
Explore the source record for details and available documents.
Animals↗
SEARCH · PubMed Health
Results for “Physostigmine”
Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.
Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.
The effects of physostigmine on cholinesterase activity, storage and release of acetylcholine in the isolated chicken heart.
Total activity of the cholinesterases (ChE) and the concentration and output of acetylcholine (ACh) were measured in isolated chicken hearts. The ACh concentration of the right ventricle was as high as that of the total heart (approximately 7 nmol/g). The ChE activity and its kinetic parameters did not differ from those of other vertebrates. In the absence of physostigmine, stimulation of both vagus nerves (20 Hz, 5 minutes) caused an output of ACh and a decrease in rate (-90% of control) and amplitude (-74%) of the ventricular contraction. Physostigmine (10(-7) M) inhibited the ChE by 87%, caused a small reduction of the ACh concentration (P = .05) and more than doubled the ACh output in response to vagal stimulation. In contrast, 10(-6) M physostigmine increased significantly the ACh concentration by about 40% within 5 minutes; the output was almost 3-fold higher than that in the absence of physostigmine and the ChE was nearly completely inhibited (-96%); the output of ACh in the 5th minute of stimulation was not significantly lower than that in the 1st minute. Physostigmine, in a concentration of 10(-4) M, did not change the ACh content of the heart and was much less effective in elevating the ACh output than was a concentration of physostigmine of 10(-6) M. In conclusion, the high ACh output from isolated chicken hearts evoked by preganglionic nerve stimulation was at least partially due to the pronounced innervation of the avian ventricles. Inhibition of the ChE by 96% failed to cause ganglionic transmission block. The formation of surplus ACh required higher physostigmine concentrations (10(-6) M) than the inhibition of the external ChE (protection of ACh released). High physostigmine concentrations (greater than 10(-6) M) counteracted the formation of surplus ACh.
Acetylcholine↗
Physostigmine: effects on cognition and affect in normal subjects.
Physostigmine was given intravenously to a total dose of 3 mg to 13 subjects; a placebo of 0.25 N saline was given intravenously to 10 other subjects; both groups received 1 mg of methscopolamine bromide subcutaneously preceding the intravenous infusions. A "physostigmine syndrome" consisting of decreased speech, slowed thoughts, mild sedation, expressionless faces, nausea, and decreased spontaneous activity was evident following doses of 1.5 to 2.0 mg of physostigmine. The capacity of short-term memory (STM) as measured by digit span tasks was significantly less for the subjects who received physostigmine than for the subjects who received placebo. No difference was observed between the two groups on tasks of consolidation from STM to long-term memory (LTM). Subjects who received physostigmine did not significantly differ from subjects who received placebo in their mood. However, two subjects in the physostigmine group, and no subjects in the saline group became tearful and depressed.
Adult↗
Physostigmine-induced contractures in frog skeletal muscle.
Physostigmine in 15 mM concentration at pH 8.4 produces reversible contractures of up to 0.3 Po tension output in frog's whole toe muscle or in 7-10 fiber bundles of these muscles, At pH 7.2, the 15 mM physostigmine contracture output is only about 0.10 Po. The 15 mM, pH 8.4 contractures are essentially unaffected by lack of external Ca2+, complete depolarization of the fibers, detubulation by glycerol treatment, and 0 degrees C ambient temperature. These results and other evidence indicate that physostigmine produces contracture by directly releasing activator Ca2+ from the sarcoplasmic reticulum (SR). Pretreatment of muscles with 4 mM procaine reduces physostigmine's capacity to produce contracture, evidently by means of a competitive inhibition at SR sites. The above results indicate similarities between physostagmine and caffeine contractures. But the physostigmine action differs in that it is reversible, and, especially, it lacks the ability, strongly characteristic of caffeine, to sensitize a muscle to produce a rapid cooling contracture. The internal action of physostigmine requires that it be permeant, and, since it is a weak base (pKa = 8.2), this property is provided by its uncharged base. But, once internal, where the pH = 6.8, most of the drug will be protonated and it may act on the SR in this form, in contrast with caffeine which, since its pKa is about 1.0, acts on the SR as uncharged base.
Animals↗
A randomized evaluation of the reversal of ketamine by physostigmine.
One hundred and eleven patients undergoing ketamine anaesthesia for therapeutic abortion were studied in a double-blind trial of the reversal of ketamine by physostigmine administered postoperatively. The results demonstrate that physostigmine does not shorten recovery time or reduce the occurrence of ketamine emergence phenomena such as hallucinations, restlessness and dreams. In fact, the recovery course was prolonged in patients given physostigmine immediately upon termination of anaesthesia as compared with controls. By contrast, when physostigmine was given 30 minutes after the last dose of ketamine, the recovery was not prolonged as compared with that of the placebo-treated controls. These findings suggest some synergism between the effects of ketamine and physostigmine and should discourage the use of physostigmine as a ketamine antidote.
Abortion, Therapeutic↗
The effect of physostigmine on normal human sleep and dreaming.
Physostigmine, an anticholinesterase that increases the action of brain acetylcholine, induces rapid eye movement (REM) sleep in normal humans. In this study we show that man dreams during physostigmine-induced REM sleep. Seventeen normal volunteers were pretreated with methscopolamine and received one intravenous infusion per night of either placebo or physostigmine either ten or 35 minutes after sleep onset. Subjects were awakened at specific times after infusion and interviewed regarding any sleep mentation prior to awakening. Results indicated that dreaming occurred during physostigmine-induced REM periods but that physostigmine did not alter mentation during non-REM sleep. These dreams were similar to spontaneous REM sleep dreams in content, vividness, unusualness, and emotionality.
Adult↗
Effects of physostigmine and lecithin on memory in Alzheimer disease.
Because there is evidence that central cholinergic mechanisms are depleted in dementia, we studied the effects of central cholinergic augmentation on the memory of 5 patients with Alzheimer disease. Patients received placebo, lecithin, physostigmine, or lecithin plus physostigmine in a double-blind study using titrated doses of the acetylcholinesterase inhibitor physostigmine. Memory was evaluated with alternate forms of the selective reminding procedure. Compared with lecithin alone, the combination of physostigmine and lecithin consistently enhanced memory storage and retrieval; physostigmine without lecithin produced no memory facilitation. The strategy of combining a cholinergic agonist and precursor holds promise, although a larger clinical trial is needed.
Aged↗
Physostigmine as an adjuvent to neuroleptanaesthesia in neurosurgical procedures.
The use of physostigmine electively to reverse the effects of droperidal and diazepam has permitted an optimum level of neuroleptanaesthesia in neurosurgical operations where co-operation of the patient is required during part of the procedure. The patient can be put to sleep or readily awakened to be fully co-operative depending on the needs of the surgeon. In this series of seven anaesthetics there were no side effects from the small doses of physostigmine employed. Bradycardia and salivation were not a problem. One child vomited once. Atropine was not necessary. Since a narcotic antagonist is not needed, a reasonable degree of analgesia can be maintained in these patients while they are awake. The latent time for the effect of physostigmine was two to four minutes and the effect of an intravenous dose lasted from 35 to 45 minutes. With physostigmine, these patients wake up gently as though from normal sleep. If neurological assessment is required post-operatively, drowsiness due to drugs can be reversed by giving more physostigmine and the level of consciousness can then be assessed.
Adjuvants, Pharmaceutic↗
Methacholine and physostigmine airway reactivity in asthmatic and nonasthmatic subjects.
Inhalation challenges using methacholine and physostigmine were performed in 3 human asthmatic and 3 nonallergic normal subjects. Plethysmographic measurements of specific airways conductance (Gaw/Vtg) were used to monitor the response. The dose required to produce a 17% fall in Gaw/Vtg was significantly lower in asthmatic subjects than in normal subjects for both physostigmine (p less than 0.0125) and methacholine (p less than 0.05). Moreover, in all subjects the relative airway sensitivity to methacholine correlated with the relative airway sensitivity to physostigmine. Both methacholine and physostigmine are cholinergic agents. Whereas methacholine acts directly at the end organ cholinergic receptor, physostigmine acts by increasing release and decreasing destruction of endogenous acetycholine at the vagal distal innervation. This suggests that the cholinergic airway hyperreactivity characteristic of asthma is a manifestation of end organ hypersensitivity.
Acetylcholine↗
The use of physostigmine as an antidote in tricyclic anti-depressant intoxication.
The value of physostigmine treatment of unconsciousness due to self-poisoning by tricyclic antidepressant drugs (TAD) was evaluated in 10 patients, and the following conclusions are drawn: 1. A slow i.v. injection of 2 mg of physostigmine produces a clear-cut increase in consciousness within 15 min if a TAD (or other drugs with central anticholingeric potencies) is mainly responsible for the poisoning. This "test dose" can give valuable diagnostic information. 2. Repeated i.v. injections seem of little practical value, since they may be expected to produce a state with rapid shifts in the level of consciousness. 3. If the test dose has a positive effect, immediate i.v. infusion of 4 mg physostigmine/h will maintain a high level of consciousness. Infusion should be stopped every sixth hour for about 30 min to check whether the level of consciousness still falls upon withdrawal of therapy 4. In cases of massive TAD overdosage, i.v. injection of physostigmine may increase the risk of grand mal seizures. 5. No signs of enhanced peripheral cholinergic activity following physostigmine are seen if 30 mg of propantheline is given i.v. every sixth hour. 6. No evidence has been produced that the morality rate in TAD poisoning is lower following physostigmine treatment whan with conventional supportive care. There must be the usual preparedness for cardiac complications.
Adult↗
Physostigmine and anesthetic requirement for halothane in dogs.
To investigate the effect of physostigmine on central nervous system (CNS) depression produced by halothane, control halothan minimum alveolar concentration (MAC) measured over 1 hour in 7 dogs was compared to MAC 30 minutes after each sequential IV dose of 0.04, 0.4, and 4 mg/kg physostigmine. MAC decreased 6.8, 11.1 (p less than 0.05), and 35.9 (p less than 0.01) percent, respectively. Six dogs were observed for an acute increase in halothane requirement in the first 30 minutes after administration of physostigmine. All 6 showed such a response at 1 or more dose levels, beginning within 1 to 5 minutes after administration and lasting 2 to 30 minutes (p less than 0.05). Five other dogs were tested with neostigmine in the same doses and showed respective decreases in MAC of 7.9, 16.6 (p less than 0.01), and 17.5 ( less than 0.01) percent. No dog showed an acute increase in anesthetic requirement. Intravenous atropine 0.5 mg/kg failed to further alter MAC after 4 mg/kg neostigmine. Physostigmine transiently antagonizes halothane anesthesia, presumably by facilitating cholinergic transmission in the CNS; neostigmine does not. After this initial response, both drugs decrease anesthetic requirement. If these data may be extrapolated to patients, they suggest that physostigmine is not an effective antagonist to postoperative somnolence due to halothane.
Animals↗
Physostigmine's effect on diminished fetal heart rate variability caused by scopolamine, meperidine and propiomazine.
Physostigmine was given to 17 patients in labor, previously given scopolamine alone or meperidine and propiomazine in combination, to ascertain its effect on reversing the loss of fetal heart rate variability caused by the administration of these drugs. The results of the study indicated that scopolamine in doses of 0.65 to 1.08 milligrams diminished fetal heart rate variability in all 7 patients and physostigmine reversed this loss of fetal heart rate variability in all 7 patients within 4 to 17 minutes after injection of the first dose of physostigmine. Similar results were noted in 10 patients with the combination of meperidine, 50 mg, and propiomazine, 20 mg. It seems tenable from this study that physostigmine does cross the placental barrier and enters the fetal circulation and that this usually occurs within 3 to 17 minutes with an average of approximately 9 minutes. In the healthy fetus the loss of fetal heart rate variability caused by scopolamine, meperidine or propiomazine can be reversed by the use of physostigmine and this reversal seems abrupt and clinically measurable on the fetal monitor print out.
Adolescent↗
Physostigmine reversal of diazepam-induced hypnosis. A study in human volunteers.
Under randomized double-blind conditions, 1.00 to 1.67 mg of intravenous physostigmine (Antilirium) reversed sleep induced by administration of 0.102 to 0.238 mg/kg body weight of intravenous diazepam in eight healthy human volunteers. Awakening occurred 330 to 740s after initiation of the physostigmine infusion at a rate of 0.5 mg/min every 4 min. Diazepam plasma levels were not significantly different at the start of either the physostigmine or placebo infusion. Physostigmine did not effect plasma binding of diazepam. Six subjects experienced nausea, and one subject developed an arrhythmia. Physostigmine reverses diazepam-induced hypnosis but causes side-effects requiring cautious administration.
Adult↗
Twitch potentiation of skeletal muscle by physostigmine at different pH.
This report extends earlier research, done with external media at pH 7.2, to new studies at pH 6.4 and 8.4 as well as 7.2, to determine the roles of the protonated and neutral forms of physostigmine (a weak base with pKalpha = 8.2) in causing twitch potentiation of the frog sartorius muscle. Physostigmine, especially at relatively high pH (8.4) and concentration (1.5 mM), considerably blocks excitation. However, the results show in general that physostigmine potentiation increased peak contraction time and thereby indicate that potentiation is occurring in terms of prolongation of the active state. At pH 6.4 and 8.4, 1 mM physostigmine causes no change in the mechanical threshold of K depolarization contractures of toe muscles, as found previously at pH 7.2. Physostigmine increasingly prolongs the action potential as pH rises, i.e., in positive correlation with the twitch potentiation, thus indicating that this electrical change is the prime determinant of the potentiation.
Action Potentials↗
Interaction of physostigmine and delta-9-tetrahydrocannabinol in man.
To investigate the hypothesis that delta-9-tetrahydrocannabinol (THC), the major psychoactive ingredient of marihuana, acts by interfering with cholinergic brain mechanisms, 0.75 to 1.25 mg of physostigmine, a centrally active cholinergic drug, was given intravenously to 5 normal volunteers who had ingested 20 to 40 mg of THC 2 hours earlier. Physostigmine decreased the degree of tachycardia and conjunctival injection produced by THC. The major psychologic effects of physostigmine were amplification of the lethargy and somnolence which occur late in the course of THC intoxication. We interpret the lack of physostigmine counteraction of the peak psychologic effects of THC as evidence against the hypothesis that THC acts predominantly by an anticholinergic mechanism.
Adult↗
Effects of scopolamine, physostigmine and chlordiazepoxide on punished and extinguished water consumption in rats.
It has been postulated that behavioral inhibition due to punishment or extinction may be mediated by brain acetylcholine, and drugs which have disinhibitory action are thought to interact with this system. This notion was tested by comparing the effects of scopolamine, physostigmine and chlordiazepoxide on punished and extinguished water consumption. Scopolamine hydrobromide (0.3, 0.5 mg/kg, i.p.), a centrally and peripherally acting antimuscarinic agent and physostigmine sulfate, (0.3 mg/kg, i.p.), a centrally and peripherally acting acetylcholinesterase inhibitor, lowered both non-punished and punishment suppressed water intake and lick rate, whereas their quaternary analogs which primarily act in the periphery, had no significant effect at comparable dose levels. Scopolamine and physostigmine suppressed punished water consumption at lower dose levels than nonpunished intake. In contrast, chlordiazepoxide (5.0, 10.0, 20.0 mg/kg, i.p.) enhanced punished as well as non-punished water intake. In a further experiment comparing punishment and extinction suppression, scopolamine and physostigmine did not affect punished or extinguished water intake; chlordiazepoxide (5.0, 10.0, 20.0 mg/kg) reliably increased punished, but not extinguished licking on the water nozzle. These results suggest (1) that scopolamine and chlordiazepoxide do not act via a common mechanism, and (2) that punishment and extinction suppression are not a pharmacological entity.
Acetylcholine↗
Studies on human memory: the interactions of diazepam, scopolamine, and physostigmine.
Seventy volunteers were injected with diazepam (0.3 mg/kg), scopolamine (8 mug/kg), or placebo, followed 70 min later by another injection of physostigmine, physostigmine and methscopolamine (in case of diazepam treatment), or placebo. Physostigmine was given in two doses, 16 and 32 mug/kg; methscopolamine, 8 and 16 mug/kg. Subjects (Ss) were tested in groups of 5 in a double blind procedure with treatments distributed according to a Latin square design. Prior to treatment, Ss heard a series of lists of words, followed by an immediate recall test. Following the first injection, delayed free recall and recognition tests were given. The second drug was then injected, followed by a presentation of another two sets of lists which were tested similarly. Subjective feelings were also evaluated with a rating questionnaire. Diazepam and scopolamine did not affect recall of information which had been learned prior to drug injection. However, both drugs impaired the learning or acquisition of new information. Physostigmine, especially in its high dose, antagonized most of the memory deficits produced by scopolamine while those of diazepam remained. This is a strong indication that scopolamine acts centrally through an anticholinergic mechanism while diazepam may act through a different system.
Adult↗
Physostigmine alters onset but not duration of REM sleep in man.
Physostigmine (1.0mg) or placebo were administered intravenously over 1-h period to seven male normal volunteers beginning 35 min after sleep onset. The results indicate that physostigmine induced the onset of REM sleep but did not significantly alter the duration of individual REM sleep periods. Physostigmine significantly shortened the REM latency and the duration of the second nonREM period. After inducing the onset of the first REM period(s); physostigmine also appeared to advance succeeding REM-nonREM sleep cycles relative to sleep onset even when the duration of each cycle was unaffected.
Adult↗