Scopolamine Subject

The utility of scopolamine in preventing motion sickness was enhanced with the development of the transdermal system that increased patient satisfaction and decreased untoward side effects. The efficacy of transdermal scopolamine, oral meclizine, and placebo in protection against motion sickness was compared in a double-blind crossover study in 36 healthy subjects. Transdermal applications were made and tablets were taken at least 12 and 2 hours before exposure to three 90-minute periods in a ship-motion simulator. Transdermal scopolamine provided better protection than placebo or meclizine, with dryness of mouth more frequently reported in the transdermal scopolamine subjects. ... 

Sagales, T., Erill, S. Domino, E. F. (1969). Differential effects of scopolamine and chlorpromazine on REM and NREM sleep in normal male subjects. Clin. Pharmacol. Then 10, 522-9. 

Poland, R. E., McCracken, J. T., Lutchmansingh, P. et al. Differential response of rapid eye movement sleep to cholinergic blockade by scopolamine in currently depressed, remitted, and normal control subjects. Biol. Psych. 41 929-938,1997. 

Scopolamine increases cerebral blood flow to lateral occipital cortex bilaterally and to the left orbitofrontal region (Grasby et al. 1995). Decreases are seen in the right thalamus, precuneus, and lateral premotor areas bilaterally. When normal subjects are chronically administered scopolamine, there is a 12% increase in cerebral blood flow on single photon emission computed tomography (SPECT), but a decrease in cerebral muscarinic binding (Sunderland et al. 1995). On the other hand, acute administration dose-dependently reduces cortical blood flow, which is maximal in frontal cortex (Gitelman and Prohovnik 1992 Prohovnik et al. 1997). 

Some functional neuroimaging studies have examined the effects of scopolamine in cognitive tasks. Although scopolamine inhibits increases in cerebral blood flow to somatosensory stimulation, it does not inhibit the neural response (Ogawa et al. 1994). Thus, cholinergic systems may be involved in coordination of cerebral blood flow increases to neural activation. Subjects performing an attentional auditory discrimination... 

Cohen RM, Gross M, Semple WE, Nordahl TE, Sunderland T. (1994). The metabolic brain pattern of young subjects given scopolamine. Exp Brain Res. 100(1) 133-43. 

Wangeman CP, Hawk MH. The effects of morphine, atropine and scopolamine in human subjects. Anesthesiology. 1942 3 24-36. 

To reveal the cognition-enhancing potential of the S-HTj antagonists, studies in age-related memory impairment have been carried out with psy-chiatrically healthy subjects impaired with scopolamine and patients with dementia. In a randomized double-blind, double-dummy, four-way crossover study in a small number of subjects, each psychiatrically healthy male subject received placebo, scopolamine [0.4 mg im], scopolamine plus alosetron [10 J,g iv], or alosetron [250 Jg] [Preston 1994 Preston et al. 1991). Assessments of verbal and spatial memory, sedation, and sustained attention were performed before and after treatment. The main results from the study were that scopolamine induced robust deficits on all primary variables measured, the reduction in verbal and spatial memories being attenuated by 10- Jg and 250- Jg doses of alosetron, respectively. No effects on the sedation or on changes in attention were noted. 

Ebert U, Oertel R, Kirch W. Influence of grapefruit juice on scopolamine pharmacokinetics and pharmacodynamics in healthy male and female subjects. Int J Clin Pharmacol Ther 2000 38(11) 523-531. 

Scopolamine and other antimuscarinic drugs produce delirium with fluctuating levels of awareness, disorientation, marked difficulty in thinking, marked loss of memory, and bizarre delusions. Most subjects, at least under experimental conditions, find these drugs to be unpleasant and have little desire to repeat the experience. 

Ahmed S, Sileno AP, deMeireles JC, DuaR, Pimplaskar HK, Xia WJ, Marinaro J, Langenback E, Matos FJ, Putcha L, Romeo VD, Behl CR (2000) Effect of pH and dose on nasal absorption of scopolamine hydrobromide in human subjects. Pharm Res 17 974-977... 

Motion sickness. Effective prophylaxis can be achieved with the parasympatholytic scopolamine (p.110) and Hq-antihistaminics (p.118) of the diphenylmethane type (e.g., diphenhydramine, meclizine). Antiemetic activity is not a property shared by all para-sympatholytics or antihistaminics. The ef -cacy of the drugs mentioned depends on the actual situation of the individual (gastric filling, ethanol consumption), environmental conditions (e.g., the behavior of fellow trav-Luellmann, Color Atlas of Pharmacology All rights reserved. Usage subject to terms... 

The isolation of atropine, scopolamine, and cocaine occurred long before the development of modern analytical techniques. Gas chromatography was the first instrumental technique available in the field of separation science and thus it is not surprising that these alkaloids were firstly analyzed by GC despite their low volatility. With the advent of capillary columns and the proliferation of various sample introduction and detection methods, GC has evolved as the dominant analytical technique for screening, identification, and quantitation of tropane alkaloids of plant origin as well as in biological fluids. The state-of-the-art of GC analysis of tropane alkaloids has been the subject of two comprehensive reviews [45,58]. We shall therefore mainly focus on publications which have appeared since 2002. 

Anticholinergic agents are typically used as treatment for anticholinesterase poisoning and vice versa. Riysostlgmlne, tetrahydroamlnoacrldlne, and other cholinesterase Inhibitors were used successfully as antidotes In several dozen subjects. The demonstration of physosclgmlne s effectiveness led to the first controlled study of Its ability to reverse delirium due to scopolamine (31). Riysosclgmlne has been used to overcome anticholinergic toxicity. 

Intravenous (1.15 pg/kg) (Scopolamine) 2 subjects Subjects with large doses experienced a rapid, severe depression of RBC Ch following agent administration. For example, volunteer 3799 (case 1385), who received 1.15 pg/kg EA 3148, showed 22% of normal RBC Ch values at 15 min after dosing and 0% after 48h this recovered to 88% of normal at 72d post -exposure. 

Subjects treated with PAMCl or Scopolamine did not have any severe drop In ChE, and there were no long lasting effects of the drug observed. 

BZ (7.4 - 14.5 pg/kg) aerosol Inhalation, 2 subjects 3834 (2 0 mg) percutaneous, 1 subject Atropine (125 pg/kg) Intramuscular, 3 subjects Prolixin (15.0 - 23.0 pg/kg) Intramuscular, 6 subjects 302668 (10.0 pg/kg) Intravenous, 1 subject 302196 (75.6 Pg/kg) oral, 1 subject TAB (90 mg total) Intramuscular, 1 subject Pretreatment with methyl scopolamine (1.0 mg) 1 subject Only 2 subjects (AlOJ) and (AlOK) who received doses of BZ and were subsequently treated with physostlgmine, showed any prolonged central effects (hallucinations, disorientation, confusion) lasting 4 to 6 days post >exposure Both subjects were asymptomatic and appeared normal when discharged from test. One subject (AlCM)) was exposed to Prolixin (23.0 pg/kg) and then treated with multiple doses (1.0 mg X 7 doses) over a 2 ay period, intramuscularly At 27 hours post-exposure, the subject complained of blurred vision, and facial expression was mask-llke, tongue "thick" and jaws open. 

Ostfeld and Aruguete (127) performed a similar study In which 54 volunteers were subjected to subcutaneous Injections of 150-800 ug of scopolamine hydrobromide. The lowest dose Induced moderate bradycardia, but decreased salivation. The highest dose completely blocked the secretion of saliva and seemed to induce sleep, hallucination, and mental disorientation more frequently chan the dose of 10 mg of atropine sulfate used by Ostfeld et al. (126). The larger doses were associated with decreased ability to perform casks requiring close accentlon. 

The subjects treated with physostlgmlne 30 min after the injection of scopolamine Improved dramatically and rapidly In their performance of the Number Facility Test. These men relapsed into delirium about 3 h after administration of physostlgmlne and then recovered at about the same rate as the untreated men. The effects of physostlgmlne on heart rate and pupil diameter were similar to those In the group treated earlier In the Intoxication. 

Baker et al. (158) summarized their studies with 82 volunteers given scopolamine. No details of the experiments or of their results were given, but the individual subjects were said to have reacted quits differently to a given dose of scopolamine. After extensive analysis of the data, the authors concluded chat research was needed to Identify the factors that cause "subject by treatment" Interactions and chat means for controlling for them were necessary for obtaining consistent effects by a given chemical. 

The combination of loss of sleep for one night and scopolamine at 10 Mg/kg had a more than additive effect on performance In the Number Facility Test and considerably more effect on manual dexterity chan the scopolamine alone. The combination also produced hallucinations In about 2.7 times as many subjects as the same dose of scopolamine alone. The results with the lover dose of scopolamine were similar to chose reported above, but less striking. The men deprived of sleep for two nights became so somnolent after the dose of scopolamine chat the tests could not be run. 

Four volunteers who had received scopolamine, three who had been given atropine, and nine who had received no chemicals Were Interviewed and examined at some unknown time after their service as experimental subjects (162). None of the subjects felt that he had suffered physical or psychic injury as a result of serving as a subject. Blood counts for all the former subjects were within the normal range. Three of the former control subjects and one former subject who had been... 

Clapper t al. (163) examined the records of eight subjects who had been given Intramuscular Injections of atropine at 62 ng/hgt six who had been given atropine at 104 Ug/kg, and six who had been given scopolamine at 11.g /ig/kg. 

The performance of each subject on the Number Facility Test after Injection was compared with his scores on the three validity scales and 10 standard scales of the Minnesota (hiltlphaslc Personality Index (MMPl). The best correlations between performance In the Number Facility Test and scores on scales In the MMPI for the men given atropine at 62 Mg/kg were with those In the h/pochondrlasls and mania scales. The best correlations for the men given atropine at 104 g/kg were with scores In the lie and mania scales. For the men given scopolamine at 11.8 pg/kg, the best correlations were with scores In the hypochondriasis and lie scales. If atropine and scopolamine are taken as representative of the group of tropic acid esters, the best Indexes of performance In the Number Facility Test under the Influence of such esters are the scores In the lie, l pochondrlasls, and mania scales of the MMPI. 

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