Details of the Drug Combination

General Information of Drug Combination (ID: DCO1DM0)

• Drug Combination Name: Glycopyrrolate + Neostigmine
• Indication: Gastrointestinal Dysfunction; Status: Phase 1 [1]
• Component Drugs:
  Glycopyrrolate (DM2M3ZA): Small molecular drug
  Neostigmine (DM6T2J3): Small molecular drug

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Glycopyrrolate

Disease Entry	ICD 11	Status	REF
Anaesthesia	9A78.6	Approved	[2]
Chronic obstructive pulmonary disease	CA22	Approved	[3]

Glycopyrrolate Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Muscarinic acetylcholine receptor M1 (CHRM1)	TTZ9SOR	ACM1_HUMAN	Antagonist	[6]

Glycopyrrolate Interacts with 1 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
Organic cation transporter 1 (SLC22A1)	DTT79CX	S22A1_HUMAN	Substrate	[7]

Indication(s) of Neostigmine

Disease Entry	ICD 11	Status	REF
Myasthenia gravis	8C6Y	Approved	[4]
Urinary retention	MF50.3	Approved	[5]

Neostigmine Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Acetylcholinesterase (AChE)	TT1RS9F	ACES_HUMAN	Inhibitor	[8]

Neostigmine Interacts with 1 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[9]

Neostigmine Interacts with 2 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Acetylcholinesterase (ACHE)	OT2H8HG6	ACES_HUMAN	Decreases Activity	[10]
Cholinesterase (BCHE)	OTOH3WQ9	CHLE_HUMAN	Affects Response To Substance	[11]

Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
Airway Reflexes, Protective	DCOIW4S	N. A.	Phase 4	[12]
Surgery	DCNJP9A	N. A.	Phase 4	[13]
Anesthesia, General	DC0I7J9	N. A.	Phase 3	[14]
Anesthesia, General	DCX75WN	N. A.	Phase 3	[14]
Surgical Procedures, Elective	DCJMR2I	N. A.	Phase 1	[15]

References

• [1] ClinicalTrials.gov (NCT02574611) Use of High Resolution Colonic Manometry in Studying Motility
• [2] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7459).
• [3] Clinical pipeline report, company report or official report of Novartis.
• [4] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [5] Neostigmine FDA Label
• [6] Autonomic cardiovascular control during a novel pharmacologic alternative to ganglionic blockade. Clin Pharmacol Ther. 2008 May;83(5):692-701.
• [7] Identification of novel substrates and structure-activity relationship of cellular uptake mediated by human organic cation transporters 1 and 2. J Med Chem. 2013 Sep 26;56(18):7232-42.
• [8] Screening of acetylcholinesterase inhibitors by CE after enzymatic reaction at capillary inlet. J Sep Sci. 2009 May;32(10):1748-56.
• [9] Improving the prediction of the brain disposition for orally administered drugs using BDDCS. Adv Drug Deliv Rev. 2012 Jan;64(1):95-109.
• [10] Hairy-root organ cultures for the production of human acetylcholinesterase. BMC Biotechnol. 2008 Dec 23;8:95.
• [11] Fresh frozen plasma transfusion for reversal of prolonged post-anaesthesia apnoea. Transfus Med. 2008 Apr;18(2):134-6. doi: 10.1111/j.1365-3148.2008.00851.x.
• [12] ClinicalTrials.gov (NCT01199237) Impact of Anesthetic Choice (Sevoflurane Versus Desflurane) on Airway Reflex Recovery in the Context of Antagonized Neuromuscular Block
• [13] ClinicalTrials.gov (NCT03939923) Role of Sugammadex as Reversal Agent in Patients Extubated Immediately After Isolated Coronary Artery Bypass Grafting Surgery
• [14] ClinicalTrials.gov (NCT00473694) Comparison of Sugammadex (MK-8616/Org 25969) With Neostigmine Administered at 1-2 Post-tetanic Counts (PTCs) After Administration of Rocuronium or Vecuronium (19.4.302/P05945/MK-8616-025)
• [15] ClinicalTrials.gov (NCT01479764) Study of Sugammadex Versus Usual Care on Incidence of Residual Blockade at Post Anesthesia Care Unit Admission (P07981)