Scopolamine

Scopolamine is a muscarinic receptor antagonist (parasympatholytic), belladonna alkaloid with a tertiary nitrogen group and a molar mass of 303.35 g-mol-1 and an average half-life of about 1.5 h. Together with atropine it occurs naturally in the nightshade plants belladonna, henbane and thorn-apple(tropane alkaloids). Scopolamine is highly soluble in water, especially in hot ethanol (Roth L 1984). Muscarinic receptor antagonists with a tertiary nitrogen group act both in the periphery and in the CNS (Graefe KH 2016).

As a muscarinic receptor antagonist, scopolamine is a competitive antagonist of acetylcholine (or other direct parasympathomimetic drugs) at the muscarinic receptor. Its effect can be reversed by high doses of a parasympathomimetic. Scopolamine already has a motor-dampening and sedative effect in therapeutic doses, inhibits salivary and sweat secretion and causes pupil dilation. In the CNS scopolamine probably leads to an inhibition of the cholinergic transmission of stimuli from the nucleus vestibularis to the higher centres of the central nervous system and from the reticular formatio to the vomiting centre.

General toxicology: Between 0.1 and 1 mg/kg central effects such as sleep, hallucinations, movement disorders, agitation and vomiting are observed in dogs (humans react to this substance like dogs). Dosage above 30 mg/kg is toxic, 50 mg/kg lethal.

Pharmacokinetic properties: Scopolamine is apparently metabolized in the liver (glucoronide or sulfate conjugation). Scopolamine is excreted with the urine.

Scopolamine is used as a transdermal patch to prevent the symptoms of motion sickness and seasickness such as dizziness, nausea and vomiting. Scopolamine is also used in the form of eye drops. It may be used as a transdermal patch in children > 10 years of age.

Pregnancy: There is limited experience in pregnant women.

Lactation: Scopolamine is excreted in breast milk but has not been shown to have any effect on breastfed children of treated women.

Fertility: There are no human data on the effects of scopolamine on female and male fertility.

Psychiatric disorders: Rare: disorientation, confusion and hallucinations.

Diseases of the nervous system: Very frequent: drowsiness, dizziness. Rarely: memory and concentration disorders, restlessness.

Eye diseases: Very common: disorders of visual accommodation (cycloplegia), including blurred vision, myopia and mydriasis (sometimes unilateral), especially when residues of active substances get from the hands into the eyes. Possible inhibition of tear secretion. For this reason, permanent contact lens wearers should ensure that their eyes are adequately moistened (artificial tear fluid). Frequently: Irritation of the eyelids. Very rarely: narrow-angle glaucoma.

Gastrointestinal disorders: Very frequent: dry mouth(xerostomia).

Skin diseases: Very rare: generalized exanthema.

Kidney and urinary tract diseases: Rarely: Micturition disorders (urinary retention).

Overdose: At higher doses, the central effects of scopolamine are similar to those of atropine. They begin with agitation, agitation and confusion, with increasing dose delirium, hallucinations and convulsions. Very high doses lead to coma and respiratory paralysis.

Treatment of poisoning: The most effective antidote is physostigmine, which should be injected slowly intravenously in doses of 1 - 4 mg (0.5 mg in children), depending on the severity of the poisoning. As physostigmine is rapidly metabolized, the patient may revert to coma within 1-2 hours, requiring further injections. Smaller doses of diazepam may be useful for arousal and convulsions. In severe cases artificial respiration may be necessary. In hyperthermia, heat dissipation (cold baths) should be provided as the most urgent measure.

With simultaneous application of scopolamine and H2-receptor blockers, an additive effect in terms of inhibition of gastric acid secretion is possible. Caution is required when scopolamine and drugs with central nervous system effects are used simultaneously; this also applies to alcohol consumption.

glaucoma; in patients with pyloric stenosis and with disorders of micturition (e.g. obstruction of flow in prostate adenomas) as well as in patients with obstruction of intestinal passage, scopolamine should be used with special caution This also applies to patients with cardiac dysrhythmia as well as with pronounced bradycardia and severe cerebral sclerosis.

Boro-Scopol® N 3 mg/g eye drops, solution;

Scopoderm TTS, transdermal patch

Side effects are listed below by system organ class and frequency. The following frequencies are used as a basis for the evaluation of adverse reactions:

• very frequent (≥ 1/10)
• frequently (≥ 1/100 to < 1/10)
• occasionally (≥ 1/1,000 to < 1/100)
• rare (≥ 1/10,000 to < 1/1,000)
• very rare (< 1/10.000)
• not known (cannot be estimated on the basis of available data).

1. Graefe KH et al muscarinic receptor antagonists. In: Graefe KH et al (Eds) Pharmacology and Toxicology. Georg Thieme Publisher Stuttgart S.114-115
2. Roth L et al (1984) Scopolamine. In: Roth L et al. (Eds) Poisonous plants, plant toxins. Nikol Publishing Company Hamburg p.921