Atropine central nervous system effects

We used an additional analysis to support the estimated LD50/ID50 ratio for BZ. Upon reviewing the LD50 of several glycolates in the mouse, it appeared that the lethality of each closely paralleled its peripheral (as reflected in heart rate changes) rather than central effects (as reflected in performance decrements). This calls into doubt the opinion, voiced in previous textbooks of pharmacology, that death from belladonnoids such as atropine results from respiratory paralysis -primarily a central nervous system effect. 

Atropine and the other tertiary agents are widely distributed in the body. Significant levels are achieved in the central nervous system within 30 minutes to 1 hour, and this may limit the dose tolerated when the drug is taken for its peripheral effects. Scopolamine is rapidly and fully distributed into the central nervous system where it has greater effects than most other antimuscarinic drugs. In contrast, the quaternary derivatives are poorly taken up by the brain and therefore are relatively free—at low doses—of central nervous system effects. 

There is an increased central nervous system (CNS) depressant effect when the skeletal muscle relaxants are administered with other CNS depressants, such as alcohol, antihistamines, opiates, and sedatives. There is an additive anticholinergic effect when cyclobenzaprine is administered with other drugs with anticholinergic effects (eg, antihistamines, antidepressants, atropine, haloperidol). See Chapter 30 for information on diazepam. 

While atropine blocks the muscarinic effects, 2-PAM regenerates cholinesterase enzymes in sympathetic, parasympathetic, and central nervous system sites. 

Atropine, an alkaloid from Atropa belladonna, is the classical parasympatholytic compound. It competes with acetylcholine for the binding at the muscarinic receptor. Its affinity towards nicotinic receptors is very low, so that it does not interfere with the ganglionic transmission or the neuromotor transmission, at least in therapeutic dosages. However, in the central nervous system muscarinic receptor do play an important role and while atropine can penetrate the blood-brain barrier it exerts pronounced central effects. Atropine, like all other antagonists of the muscarinic acetylcholine receptor inhibit the stimulatory influence of the parasympathetic branch of the autonomous nervous system. All excretory glands (tear, sweat, salivary, gasto-intestinal, bronchi) are... 

Mechanism of Action Competitive inhibitors of the muscarinic actions of acetylcholine, acting at receptors located in exocrine glands, smooth and cardiac muscle, and intramural neurons. Composed of 3 main constituents atropine, scopolamine, and hyoscyamine. Scopolamine exerts greater effects on the CNS, eye, and secretory glands than the constituents atropine and hyoscyamine. Atropine exerts more activity on the heart, intestine, and bronchial muscle and exhibits a more prolonged duration of action compared to scopolamine. Hyoscyamine exerts similar actions to atropine but has more potent central and peripheral nervous system effects. TherapeuticEffect Peripheral anticholinergic and antispasmodic action, mild sedation. Pharmacokinetics None known... 

It soon became evident that no available antidotes could block the pharmacologic activity of these chemicals, alleviate the signs and symptoms of toxicity, or restore normal bodily functions after exposure. Atropine readily antagonized the muscarinic actions, including those in the central nervous system (CNS), but elicited no reversal of the nicotinic effects. Better forms of therapy were sought, particularly to alleviate the nicotinic effects of anticholinesterase agents. 

Loperamide is similar in action and use to diphenoxylate however, it does not need to be formulated with atropine and is available by prescription and OTC. It is reported to have fewer central nervous system side effects than diphenoxylate. 

The modes of action of different alkaloids are diverse. For example, nicotine binds to and affects nicotinic acetylcholine receptors and shows toxicity. A recent molecular 3D model suggests that both acetylcholine and nicotine bind to the same pocket formed in a nicotinic acetylcholine receptor.15 Morphine binds to and activates opioid receptors, transmembrane-spanning G protein-coupled receptors, in the central nervous system of humans.16 Caffeine, which is structurally similar to adenine, inhibits cyclic AMP phosphodiesterase activity and inhibits the degradation of cAMP, thus exerting a toxic effect on insects 17 in human beings, binding of caffeine to the adenosine A2A receptor induces wakefulness.18 Atropine binds to muscarinic acetylcholine receptors, competing with acetylcholine, and blocks neurotransmission.1... 

---