Scopolamine effective dose

Previously published clinical observations of daily atropine and scopolamine effects usually did not include precise recording time of onset and recovery from each dose. At least one journal report, however, did note that a certain degree of tolerance to atropine developed in the course of daily use for several months or years. This may or may not be based on a mechanism similar to the second-dose effect that we observed with BZ. Conceivably, this might have military implications if the target population had previously been exposed to an attack with BZ on one or more occasions. The practical significance of the slightly earlier onset and recovery, however (Fig. 12), seems to be relatively minor. 

The effects of mechylscopolammonium bromide and atropine sulfate on heart rate became evident (18-19 min) and reached their greatest intensities (37-40 min) at about the same times, despite the fact chat the dose of mechylscopolammonium bromide was only 22 5% chat of atropine sulfate. When equally effective doses of the compounds were administered, methylscopolammonlum bromide was slower chan scopolamine hydrobromide and atropine sulfate in exerting its maximal effect on salivation and on Che iris The effects of scopolamine l drobromide on the iris and on accommodation for near vision lasted considerably longer than those of equal doses of methylscopolammonltim bromide and atropine sulfate. 

Oliverio, A. (1967) Contrasting effects of scopolamine on mice trained simultaneously with two different schedules of avoidance conditioning. Psychopharmacologia (Berl.), 11, 39-51. Thompson, W. R. (1947) Use of moving averages and interpolation to estimate median-effective dose. 

However, responses to administration of a cholinergic blocking drug vary and often depend on the drug and the dose used. For example, scopolamine may occasionally cause excitement, delirium, and restlessness. This reaction is thought to be a drug idiosyncrasy (an unexpected or unusual drug effect). 

Buclizine may be taken without water. The patient is instructed to place the tablet in the mouth and allow it to dissolve or to chew or swallow the tablet whole. When given for motion sickness, one 50-mg dose is usually effective. For more extensive travel, a second 50-mg dose may be taken alter 4 to 6 hours. When administering scopolamine, one transdermal system is applied behind the ear approximately 4 hours before the antiemetic effect is needed. About 1 gof scopolamine will be administered every 24 hours for 3 days. If the disk detaches from the body, discard it and place a fresh one behind the opposite ear. (See Fhtient and Family Teaching Checklist Applying Transdermal Scopolamine.)... 

In contrast to the nicotinic antagonists and indeed both nicotinic and muscarinic agonists, there are a number of muscarinic antagonists, like atropine, hyoscine (scopolamine) and benztropine, that readily cross the blood-brain barrier to produce central effects. Somewhat surprisingly, atropine is a central stimulant while hyoscine is sedative, as least in reasonable doses. This would be the expected effect of a drug that is blocking the excitatory effects of ACh on neurons but since the stimulant action of atropine can be reversed by an anticholinesterase it is still presumed to involve ACh in some way. Generally these compounds are effective in the control of motion but not other forms of sickness (especially hyoscine), tend to impair memory (Chapter 18) and reduce some of the symptoms of Parkinsonism (Chapter 15). 

Parrott AC (1986). The effects of transdermal scopolamine and four dose levels of oral scopolamine (0.15, 0.3, 0.6, and 1.2mg) upon psychological performance. Psychopharmacology, 89(3), 347-354. 

Atropine generally increases heart rate, but it may briefly and mildly decrease it initially, due to Ml receptors on postganglionic parasympathetic neurons. Larger doses of atropine produce greater tachycardia, due to M2 receptors on the sinoatrial node pacemaker cells. There are no changes in blood pressure, but arrhythmias may occur. Scopolamine produces more bradycardia and decreases arterial pressure, whereas atropine has little effect on blood pressure (Vesalainen et al. 1997 Brown and Taylor 1996). 

Sagales T, Erill S, Domino EF. (1975). Effects of repeated doses of scopolamine on the electroencephalographic stages of sleep in normal volunteers. Clin Pharmacol Ther. 18(06) ITJ-yi. Sanders-Bush E, Burris KD, Knoth K. (1988). Lysergic acid diethylamide and 2,5-dimethoxy-4-methylamphetamine are partial agonists at serotonin receptors linked to phosphoinositide hydrolysis. J Pharmacol Exp Ther. 246(3) 924-28. 

Atropine, increases, but scopolamine actually decreases, heart rate at low doses and at higher doses it does not produce elevations as high as atropine at the ID50 (Fig. 64). This is probably attributable to medullary mechanisms that tend to reduce heart rate. Similar effects also occur with atropine but they are quickly overwhelmed by atropine s much greater peripheral potency. (Low dose studies of atropine reveal this more clearly.) Note that the duration of scopolamine s effects is very similar to that of atropine. 

Scopolamine Potentiation of High Dose Central Effects by Chlorpromazine (CPZ)... 

Goodman noted that the usual textbook estimates of the lethal dose of atropine (and scopolamine) are undoubtedly too low. With respect to scopolamine, for example, he found 9 cases that survived scopolamine doses of 225-267 mg, 3 cases that survived 324-384 mg and 2 who survived 500 mg.. (Abood also reported personal observation of two recoveries from large oral doses of scopolamine 350 mg and 500 mg, respectively.) These doses are close to the highest reported lethal range for atropine. Since scopolamine has about 7x the potency of atropine centrally, but roughly equal potency peripherally, one can infer that death from belladonnoid drugs is probably due to a peripheral effect - most likely cardiotoxicity. 

The biological activity of flavonoids has attracted much interest in the part twenty years and a few compounds of this class have been shown to have AChEI effects. The flavanone naringenin (74) from Citrus junos (Rutaceae) ameliorated scopolamine-induced amnesia in mice, which may be related to an antiAChE effect, since naringenin was shown to inhibit AChE in vitro dose dependently. A recent theoretical study has shown that flavonoids and xanthones exhibit polyvalent effects such as antioxidant, amyloid reduction and cholinesterase inhibition, which made them interesting candidates for further studies. 

Belladonna alkaloids have an extremely broad pharmacological spectrum. In addition to their ability to block M-receptors, atropine and scopolamine also act on other receptors, thus showing corresponding effects. They can only block nicotinic cholinergic receptors, however, in significantly larger doses than those used in clinics. Atropine also exhibits properties of local anesthetics and histamine (Hj) receptor blockers. Atropine and... 

Although atropine and scopolamine share many properties, an important difference is the easier entry of scopolamine into the CNS. Typical doses of atropine (0.2-2 mg) have minimal central effects, while larger doses can produce a constellation of responses collectively termed the central anticholinergic syndrome. At intermediate doses (2-10 mg), memory and concentration may be impaired, and the patient may be drowsy. If doses of 10 mg or more are used, the patient may exhibit confusion, excitement, hallucinations, ataxia, asyn-ergia, and possibly coma. 

Even low doses of scopolamine have central effects. Sedation, amnesia, and drowsiness are common during the clinical use of this drug. Large doses of scopolamine can produce all of the responses seen with atropine. Other tertiary amine compounds with muscarinic receptor blocking activity have similar central effects. 

Antimuscarinic drugs block contraction of the iris sphincter and ciliary muscles of the eye produced by ACh. This results in dilation of the pupil (mydriasis) and paralysis of accommodation (cycloplegia), responses that cause photophobia and inability to focus on nearby objects. Ocular effects are produced only after higher parenteral doses. Atropine and scopolamine produce responses lasting several days when applied directly to the eyes. 

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. 

Wernicke JF, Dunlop SR, Dornscif BE, et al Fixed-dose fluoxetine therapy for depression. Psychophaimacol Bull 23 164-168, 1987 Wernicke JF, Dunlop SR, Dornscif BE, et al Low dose fluoxetine therapy for depression. Psychopharmacol Bull 24 183-188, 1988 Wesnes K, Revell A The separate and combined effects of scopolamine and nicotine on human information processing. Psychopharmacology 84 5-11, 1984 Wesnes K, Warburton D Smoking, nicotine, and human performance. Pharmacol Ther 21 189-208, 1983... 

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