Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.1.8 (cholinesterase)
 12,691 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The evidence for the involvement of cholinergic muscarinic receptors in mania and depression is reviewed. Small pilot trials with cholinesterase inhibitors and muscarinic agonists suggest that stimulation of muscarinic receptors may produce an antimanic effect, possibly by activation of muscarinic M(4) receptors. It is concluded that it is not likely that currently used mood stabilizers, such as lithium, valproic acid and carbamazepine, work directly through muscarinic receptor mechanisms. Furthermore, the evidence indicates that antipsychotic agents used for mania are working through the common mechanism of antagonism of dopamine D(2) receptors, and interactions with muscarinic receptors do not play a key role. Finally, it is hypothesized that olanzapine has robust antimanic activity, due to blockade of dopamine D(2) receptors and antagonism of other monoaminergic receptors. Olanzapine may normalize mood due to antidepressant-like activities, such as 5-HT(2A) receptor antagonism and increasing cortical norepinephrine and dopamine.
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PMID:Role of the cholinergic muscarinic system in bipolar disorder and related mechanism of action of antipsychotic agents. 1198 96

Neuroleptic malignant syndrome (NMS) is an idiosyncratic and uncommon but serious adverse effect that has been reported with both typical and atypical antipsychotic agents. We describe a 58-year-old man with Down syndrome and dementia who was receiving low-dose olanzapine and rivastigmine therapy; he developed NMS 4 months after starting olanzapine. The patient presented with altered mental status, rigidity, fever, diaphoresis, and tremor, and his creatine kinase level was elevated. Olanzapine was discontinued, and the patient fully recovered; antipsychotic therapy was not restarted. Based on the Naranjo adverse drug reaction probability scale, olanzapine was the probable cause of the patient's NMS. In addition, use of rivastigmine in combination with olanzapine may have placed the patient at greater risk for NMS, possibly due to an acetylcholine-dopamine imbalance. Clinicians should be aware of the potential for NMS even with low doses of antipsychotics, particularly in patients who have a limited ability to communicate. Concomitant administration of cholinesterase inhibitors such as rivastigmine may represent an unrecognized risk factor for NMS development.
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PMID:Olanzapine-associated neuroleptic malignant syndrome in a patient receiving concomitant rivastigmine therapy. 1829 20

Scopolamine, a non-selective muscarinic receptor antagonist has widespread central nervous system effects. Muscarinic receptors located in the central nervous system play a vital role in the modulation of impulsivity. The objective of the current study was to evaluate the effect of scopolamine on impulsivity using differential-reinforcement-of-low-rate 72-s schedule (DRL-72s) and to demonstrate the involvement of serotonergic receptors in mediating the effect of olanzapine (atypical antipsychotic) on scopolamine induced impulsivity. Scopolamine impaired the performance of the rats trained under DRL-72s schedule. Olanzapine reversed the deficits induced by scopolamine. We evaluated the effect of donepezil (cholinesterase inhibitor), SB-742457 (5-HT6 and 5-HT2a antagonist), and haloperidol (typical antipsychotic) in rats challenged with scopolamine in the DRL-72s schedule to identify the receptor(s) involved in reversing the deficits. SB-742457 partially reversed the deficits, but donepezil and haloperidol did not show any effects on the deficits induced by scopolamine. Olanzapine and SB-742457 shifted the peak location (PkL) towards longer IRT duration, indicating a decrease in motor impulsivity. Modulation of scopolamine-induced impulsivity by olanzapine could be partly due to its antagonistic action at 5-HT2a and 5-HT6 receptors, respectively. Superior effects of olanzapine on impulsivity in schizophrenic patients may be mediated through the antagonism of 5-HT2a and 5-HT6 receptors.
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PMID:Effect of olanzapine on scopolamine induced deficits in differential reinforcement of low rate 72s (DRL-72s) schedule in rats: involvement of the serotonergic receptors in restoring the deficits. 2413