Analgesic and antineuropathic drugs acting through central cholinergic mechanisms.
Article Details
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Bartolini A, Di Cesare Mannelli L, Ghelardini C
Analgesic and antineuropathic drugs acting through central cholinergic mechanisms.
Recent Pat CNS Drug Discov. 2011 May 1;6(2):119-40.
- PubMed ID
- 21585331 [ View in PubMed]
- Abstract
The role of muscarinic and nicotinic cholinergic receptors in analgesia and neuropathic pain relief is relatively unknown. This review describes how such drugs induce analgesia or alleviate neuropathic pain by acting on the central cholinergic system. Several pharmacological strategies are discussed which increase synthesis and release of acetylcholine (ACh) from cholinergic neurons. The effects of their acute and chronic administration are described. The pharmacological strategies which facilitate the physiological functions of the cholinergic system without altering the normal modulation of cholinergic signals are highlighted. It is proposed that full agonists of muscarinic or nicotinic receptors should be avoided. Their activation is too intense and un-physiological because neuronal signals are distorted when these receptors are constantly activated. Good results can be achieved by using agents that are able to a) increase ACh synthesis, b) partially inhibit cholinesterase activity c) selectively block the autoreceptor or heteroreceptor feedback mechanisms. Activation of M(1) subtype muscarinic receptors induces analgesia. Chronic stimulation of nicotinic (N(1)) receptors has neuronal protective effects. Recent experimental results indicate a relationship between repeated cholinergic stimulation and neurotrophic activation of the glial derived neurotrophic factor (GDNF) family. At least 9 patents covering novel chemicals for cholinergic system modulation and pain control are discussed.
DrugBank Data that Cites this Article
- Drug Targets
Drug Target Kind Organism Pharmacological Action Actions Metoclopramide 5-hydroxytryptamine receptor 4 Protein Humans YesAgonistDetails Metoclopramide Dopamine D2 receptor Protein Humans YesAntagonistDetails