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Colorimetric and gas-liquid chromatographic determination of atropine-hyoscyamine and hyoscine (scopolamine) in solanaceous plants.

Two colorimetric micromethods are described for the determination of atropine-hyoscyamine and hyoscine (scopolamine), using p-dimethylaminobenzaldehyde and citric acid-acetic anhydride as the color reagents. These methods are sensitive to 60-1200 and 10-360 mug alkaloid/10 ml. The colorimetric methods were also successfully applied after a preliminary thin layer chromatographic separation of the alkaloids. A gas-liquid chromatographic procedure was also developed, which yielded comparable results with the colorimetric methods.

Atropine↗

Central action of drugs acting on the cholinergic muscarinic receptor. III. Influence of atropine and scopolamine injected intraventricularly on behavior and levels of biogenic amines in the rat brain.

Atropine (At) and scopolamine (Sc) in low doses intensify basic activity, increase amphetamine stereotypy, and suppress catalepsy induced by injection of haloperidol. High doses lower body temperature, antagonize amphetamine stereotypy, and intensify the hypnotic action of chloral hydrate. Doses of about 1/2 LD50 induce narcotic sleep. Both At and Sc in a wide range of dosage protect against the tonic phase of convulsions produced by electroshock. Sc depresses content of acetylcholine in the brain proportionally to its dosage; At had a similar effect only at the lower of the two doses that were used. Both compounds had no effect on levels of noradrenaline and dopamine in the brain. The results indicate that low doses of blockers of the cholinergic muscarinic receptor, injected intraventricularly, produce strong central stimulation, whereas high doses produce depression of the central nervous system.

Acetylcholine↗

Continuous cocaine induces persisting changes in behavioral responsivity to both scopolamine and diazepam.

Forty-eight male rats were administered continuous cocaine, daily cocaine injections (intermittent), continuous amphetamine, or no drug for 5 days. Beginning 45 days after the administration all groups were tested for their responsivity, as measured by automated activity cages, to a low dose of the cholinergic agonist scopolamine. The continuous cocaine group showed decreased sensitivity to this challenge as compared to the other groups. When tested with a low dose of diazepam, the continuous cocaine group showed the greatest response. However, when observed following an injection of cocaine HCl, the intermittent cocaine group showed the greatest behavioral response. These findings support those of previous studies that indicated that the mode of initial cocaine administration is a key factor in the production of persisting changes in behavior and biochemistry.

Amphetamine↗

Differential effects of intracerebroventricular AF64A injection, nucleus basalis of Meynert lesion, and scopolamine on place navigation and open-field behavior of rats.

The present study was conducted to compare the behavioral effects of intracerebroventricular AF64A injection, electrolytic lesion of the nucleus basalis of Meynert (NBM), and systemic scopolamine treatment, all of which are typical experimental models of central cholinergic system dysfunction, on place navigation performance and open-field behavior in rats. The animals were trained in a circular pool to escape from opaque water onto the hidden platform fixed at a particular location for 5 days. Significant performance deficits were observed in all the models tested. However, it is of importance that any impairments relating to information storage within a day or across days were not obtained. Choline acetyltransferase activity was decreased in the hippocampus of AF64A-injected rats and in the cortex of NBM-lesioned rats, respectively, but those changes did not simply associate with the reductions of the performance. These results suggest that the central cholinergic system is only partially involved in cognitive process. In the open-field test, ambulation, rearing, defecation, and urination were measured for 5 min. Patterns of changes in the open-field behavior were clearly different among the 3 models, indicating variability of the effects of these cholinergic manipulations on motor activities and emotionality.

Animals↗

Circadian effects of scopolamine on memory, exploratory behavior, and muscarinic receptors in mouse brain.

Mice were maintained at light-dark cycle with lights on from 05:00-19:00 for 10 d in laboratory. The study was performed at 07:00-09:00, 15:00-17:00, and 21:00-23:00 in June and July. Scopolamine (Scop, 0.1 and 0.4 mg.kg-1, ip) was injected 15 min prior to training or the first exploratory test. The amnesic effects of Scop showed hyperresponses at 07:00-09:00 and 15:00-17:00, and hyporesponses at 21:00-23:00 using step-through and step-down tasks. The circadian effects of Scop on exploratory behavior were consistent with the findings above mentioned. The numbers of [3H]quinuclidinyl benzilate ([3H]QNB) binding sites in the temporal cortex and hippocampus were more at 08:00 and 16:00 than those at 22:00. However, muscarinic receptor levels in the striatum were lower at 08:00 than those at 22:00. These results indicated that the effects of Scop on memory, behavior in a novel environment, and muscarinic receptors in brain regions showed circadian changes in mice.

Animals↗

Behavioral sensitivity to amphetamine or scopolamine after acute administration of nicotine in the rat.

OBJECTIVES: Earlier experiments have revealed that a single pretreatment of the rat with chlorphenvinphos (CVP) at a subtoxic dose (1.0 mg/kg, about 1/10 of DL50) makes the animal hyposensitive to the locomotor stimulating effect of amphetamine (AMPH) or scopolamine (SCOP) given three weeks postexposure. Such a hyposensitivity did not develop after a single or multiple (at short intervals) dosing with oxotremorine (OXO), a direct muscarinic agonist, which suggests that it was not mediated by muscarinic receptors. The purpose of the present experiment was to find out whether activation of nicotinic receptors could induce behavioral hyposensitivity to AMPH. MATERIALS AND METHODS: Male adult Wistar rats were pretreated once with 0.00, 0.5 or 1.0 mg/kg of nicotine (NIC), a nicotinic agonist, and challenged 15 days later with 1.0 mg/kg of AMPH or 0.75 mg/kg of SCOP. The pre- and postdrug open-field behavior of the rats was measured using a computerized set of activity meters. RESULTS: Pretreatment with NIC, like pretreatment with OXO, did not make the animals hyposensitive to AMPH or SCOP. In a preliminary experiment we have also found that rats do not develop hyposensitivity to AMPH and SCOP after pretreatment with physostigmine, a reversible anticholinesterase and a direct nicotinic and possibly muscarinic agonist. CONCLUSIONS: The results suggest that a transient overstimulation of the cholinergic system cannot be the cause or a sufficient condition for the development of the CVP-induced diminution of sensitivity to AMPH and SCOP.

Amphetamine↗

Amphetamine- and scopolamine-induced locomotor activity following treatment with chlorphenvinphos or chlorphyriphos in rats.

OBJECTIVES: Effects of acute exposure to organophosphorous pesticides (OPs), chlorphenvinphos (CVP) or chlorphyriphos (CPF) on amphetamine (AMPH)- or scopolamine (SCOP)-induced open-field locomotion were compared in rats. MATERIALS AND METHODS: CVP and CPF were administered intraperitoneally, both at doses resulting in about 50% inhibition of erythrocyte acetylcholinesterase (rbcAChE). The pesticide groups did not differ one from another in the magnitude of the acute behavioral effects. RESULTS: Three weeks after the exposure, i.e. when AChE activity returned to normal level, the behavioral response to AMPH and SCOP was significantly reduced in CVP-, but not in CPF-pretreated rats. CONCLUSIONS: These results confirm that a single exposure to organophosphorous pesticides may result in neurobehavioral effects detectable after restitution of AChE. They also show that CVP and CPF differ in respect of long lasting functional consequences of exposure, which suggests a difference in the mechanism of toxicity.

Acetylcholinesterase↗

Results of toxicological investigations of poisonings with atropine and scopolamine.

Lethal poisonings with alkaloids are rarely observed in the Federal Republic of Germany. We had however to investigate a case of poisoning with atropine and another with scopolamine during the last few years. The analysis was carried out with GC-MS and HPLC. Concentrations of the active substance on different organs of the body are represented. Thus the amount of alkaloid being taken is deduced. Cause of death is discussed by means of literature data.

Acquired Immunodeficiency Syndrome↗

[Effects of scopolamine on delayed matching and non-matching to sample responses in T-maze in rats].

The present study was designed to investigate the effects of scopolamine (SCP; 0.25 and 0.5 mg/kg, ip) on delayed matching and non-matching to sample (DMTS and DNMTS) responses in T-maze in rats. The groups consisted of the animals (N = 14) trained on the DMTS task with a short (3 min) intertrial interval (ITI), those (N = 12) on the DNMTS task with the short ITI, and those (N = 25) on the DNMTS task with a long (20 min) ITI. The results showed that (1) the DMTS task required a significantly larger number of trials to acquire than the DNMTS task, (2) the decay of performance with delay between information and choice runs was more pronounced in DMTS than in DNMTS, (3) the number of correct choices was smaller in the DNMTS responses with the short ITI than in those with the long ITI, (4) the disruptive effects of SCP were more marked in the DMTS than DNMTS responses, and (5) the effects of SCP in the DNMTS responses with the short ITI were not different from those in the responses with the long ITI. These results were discussed in terms of innate response (win-shift and win-stay) strategy, and working and reference memory components. It was concluded that SCP exerted the detrimental effects on both working and reference memory components.

Animals↗

[Transdermal scopolamine and mydriasis].

The authors report five cases of mydriasis induced by the use of transdermal scopolamine delivery systems. Anisocoria and narrow angle glaucoma were involved in four cases; in one case, the use of a strong dosage resulted in a bilateral mydriasis in a child.

Administration, Cutaneous↗

The role of body turn-brightness associations in the effect of scopolamine on response-to-change in the rat.

We explored further the different effects of anticholinergics on response-to-change in the passive and active tests. We hypothesized that body turn-brightness associations are formed in the active but not in the passive test, where the turns were prevented by transparent partitions blocking maze arm entrance. This difference might account for the resistance of the active test performance to anticholinergic drugs. To examine this idea, the passive test conditions were modified so that body turns were possible. However, scopolamine (1.0 mg/kg) interfered with response-to-change performance to the same extent as observed previously in the typical passive test procedure. Thus, body turn-brightness associations are not the source of resistance of active test performance to cholinergic receptor blockade.

Animals↗

[Action of PMA (phorbol myristate acetate), scopolamine, propranolol, and oxotremorine on memorization of an active or passive avoidance test].

The role of various second messengers in the learning and retention of a passive or active avoidance has been investigated in mice. Scopolamine at 3 mg/kg i.p. inhibits muscarinic M1 and M2 receptors and thus acetylcholine activation of the phosphoinositide cycle. This results in amnesia of passive avoidance but has no effect on active avoidance learning. Oxotremorine at 0.05 mg/kg i.p., whose preferential M2 muscarinic action limits acetylcholine release and also inhibits adenylate cyclase activity, causes amnesia of the retention of a passive avoidance and antagonizes the learning of an active avoidance. DL-propranolol at 40 mg/kg i.p., which inhibits cAMP formation, does not affect retention of a passive avoidance but antagonizes that of an active avoidance. Similarly, phorbol myristate acetate a 0.1 mg/kg i.p., which activates protein kinase C, has no effect on the retention of a passive avoidance but antagonizes that of an active avoidance. The results tend to show a distinct role for cAMP-dependent protein kinase, which would participate in memorization processes of an active avoidance, and for protein kinase C, which would participate in that of a passive avoidance. The authors discuss the involvement of different neurophysiological mechanisms as a function of the type of behavior, depending on whether or not it is related to the control of environmental situations.

Acetylcholine↗

[Comparative in-flight study of a scopolamine-containing membrane plaster versus dimenhydrinate under defined acceleration conditions].

The efficacy and tolerability of Scopoderm TTS (SCOTTS), a transdermal system containing scopolamine, were compared with those of the oral antiemetic dimenhydrinate (double-dummy technique) in a controlled, double-blind, within-patient study including 20 test persons with proven motion sickness. During a 1-h test flight, SCOTTS proved to be as effective as dimenhydrinate. The efficacy and tolerability of both SCOTTS and dimenhydrinate were assessed as to be equally good. Due to its galenic properties, SCOTTS is effective over a 72-h period and therefore is useful in the prevention of motion sickness during long-distance flights, where it is superior to dimenhydrinate.

Acceleration↗

[Morphine and scopolamine in premedication. A comparison of peroral and transdermal administration with intramuscular injections].

A randomized clinical study was undertaken to compare the feasibility and effectiveness of two different premedications. Thirty-eight patients admitted for elective tonsillectomy gave informed consent and were randomly assigned to two groups. One group received morphine orally and scopolamine transdermally. In the second group, the same substances were applied intramuscularly before the operation. The following parameters were evaluated: psychological state, sedation, hemodynamics, salivation, pain and side effects. General anesthesia was maintained with thiopental, fentanyl, N2O/O2, and enflurane; alcuronium was used for muscle relaxation. The results showed no significant differences between the groups for any of the parameters considered.

Administration, Oral↗

The effects of swallowing frequency and transdermal scopolamine on esophageal acid clearance.

Fourteen volunteers were studied on two occasions to assess the effect of swallowing frequency on acid clearance time. The experimental protocol consisted of two trials of infusion of 15 ml of 0.1 N HCl into the distal esophagus. One trial required swallowing every 30 s for 10 min. The other trial involved an initial rapid swallowing rate (seven swallows in the 1st min) with a gradual predetermined decline in rate. This procedure was repeated 12 h after application of a transdermal scopolamine patch. Baseline clearance times for rapid and slow swallowing were not significantly different. The anticholinergic drug significantly prolonged the clearance times for both rapid and slow swallowing. Under baseline conditions, sequential swallows (after the first three to four swallows) produced a significant rise in pH until the clearance criterion of pH 4.0 was reached. This effect was abolished with the anticholinergic drug. These results support a two-stage model of acid clearance with initial volume clearance and subsequent salivary buffering of residual intraesophageal acid.

Administration, Topical↗

[Analysis and stability of atropine sulfate and scopolamine hydrobromide. 2. Quantitative determination of the alkaloid in its decomposition product; 79. contribution to problems concerning the use of plastic containers for liquid pharmaceuticals].

The authors describe a method which permits, after thin-layer chromatographic separation and elution by means of the Eluchrom apparatus, to determine the tropane alkaloids and apoatropine in the presence of their decomposition products using tropaeolin 00. The recommended method has proved to be superior to other elution variants with regard to accuracy and reproducibility. Detectable amounts (microgram/ml): atropine, 0.4-4.0; scopolamine, 1.2-7.2; apoatropine, 0.8-3,2.

Atropine↗

[Analysis and stability of atropine sulfate and scopolamine hydrobromide. 3: Studies on the stability of tropane alkaloids; 80: contribution to problems in the use of plastic containers for liquid pharmaceuticals].

On evaluating their investigations, the authors discuss the degradation mechanism of tropane alkaloids in aqueous solution. As evidenced by competitive and consecutive reactions (hydrolysis, dehydration, dimerization), the degradation mechanism is characterized by a complicated course. Apart from temperature, a series of other factors, above all the pH value, exerts a considerable effect on the stability of both the alkaloids. Unbuffered solutions are more stable than buffered ones. The isothermal short-time test is not suitable for stability prediction. In the long-time test it was found that unbuffered aqueous atropine sulphate solutions still contained 90% of their initial drug content after 18 months' storage in low-density polyethylene containers at 20 degrees C. Scopolamine hydrobromide solutions showed an almost analogous behaviour. Of the container materials tested, low-density polyethylene bottles have been found to be best suited.

Atropine↗