Details of Drug Interaction | MecDDI

Drug General Information (ID: DDI087FODY)
Drug Name			Physostigmine (ophthalmic)		Drug Info		Clomipramine		Drug Info
Drug Type		Small molecule				Small molecule
Therapeutic Class		Ophthalmic Glaucoma Agents/Antidotes				Antidepressants
Structure

Mechanism of Physostigmine (ophthalmic)-Clomipramine Interaction (Severity Level: Moderate)
Antagonize the effect of cholinergic agents Click to Show/Hide Mechanism Graph

Drug Name		Physostigmine (ophthalmic)				Clomipramine
Mechanism		Cholinergic effects Acetylcholinesterase Inhibitor				Anticholinergic effects Muscarinic acetylcholine receptor Antagonist
Key Mechanism Factor 1
		Factor Name		Acetylcholinesterase				× Structure Sequence MRPPQCLLHTPSLASPLLLLLLWLLGGGVGAEGREDAELLVTVRGGRLRGIRLKTPGGPVSAFLGIPFAEPPMGPRRFLPPEPKQPWSGVVDATTFQSVCYQYVDTLYPGFEGTEMWNPNRELSEDCLYLNVWTPYPRPTSPTPVLVWIYGGGFYSGASSLDVYDGRFLVQAERTVLVSMNYRVGAFGFLALPGSREAPGNVGLLDQRLALQWVQENVAAFGGDPTSVTLFGESAGAASVGMHLLSPPSRGLFHRAVLQSGAPNGPWATVGMGEARRRATQLAHLVGCPPGGTGGNDTELVACLRTRPAQVLVNHEWHVLPQESVFRFSFVPVVDGDFLSDTPEALINAGDFHGLQVLVGVVKDEGSYFLVYGAPGFSKDNESLISRAEFLAGVRVGVPQVSDLAAEAVVLHYTDWLHPEDPARLREALSDVVGDHNVVCPVAQLAGRLAAQGARVYAYVFEHRASTLSWPLWMGVPHGYEIEFIFGIPLDPSRNYTAEEKIFAQRLMRYWANFARTGDPNEPRDPKAPQWPPYTAGAQQYVSLDLRPLEVRRGLRAQACAFWNRFLPKLLSATDTLDEAERQWKAEFHRWSSYMVHWKNQFDHYSKQDRCSDL
		Gene Name		ACHE
		Uniprot ID		ACES_HUMAN
		KEGG Pathway		hsa:43
		Protein Family		Type-B carboxylesterase/lipase family
		Protein Function		Hydrolyzes rapidly the acetylcholine neurotransmitter released into the synaptic cleft allowing to terminate the signal transduction at the neuromuscular junction. Role in neuronal apoptosis. Click to Show/Hide
Key Mechanism Factor 2
		Factor Name		Muscarinic acetylcholine receptor M				Structure Sequence
		Protein Family		G-protein coupled receptor 1 family
		Protein Function		The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins. Primary transducing effect is Pi turnover. Click to Show/Hide
Mechanism Description		Antagonize the effect of Physostigmine (ophthalmic) when combined with Clomipramine

Recommended Action
Management		Patients receiving long-term therapy with anticholinergic agents should be monitored for potentially diminished therapeutic (miotic) response to ophthalmic cholinergic therapy, and dosages adjusted as necessary.

References
1	Multum Information Services, Inc. Expert Review Panel.
2	Product Information. Pilopine HS (pilocarpine ophthalmic). Alcon Laboratories Inc, Fort Worth, TX.