Details of the Drug-Related molecule(s) Interaction Atlas

General Information of Drug (ID: DM09Z35)

• Drug Name: bilobalide Drug Info
• Synonyms: Bilobalide; 33570-04-6; Bilobalid; (-)-Bilobalide; UNII-M81D2O8H7U; CHEBI:3103; M81D2O8H7U; Bilobalide A; 4H,5aH,9H-Furo(2,3-b)furo(3',2':2,3)cyclopenta(1,2-c)furan-2,4,7(3H,8H)-trione, 9-(1,1-dimethylethyl)-10,10a-dihydro-8,9-dihydroxy-, (5aR-(3aS*,5aalpha,8beta,8aS*,9alpha,10aalpha))-; (3aS,8R,8aS,9R,10aS)-9-tert-butyl-8,9-dihydroxydihydro-9H-furo[2,3-b]furo[3',2':2,3]cyclopenta[1,2-c]furan-2,4,7(3H,8H)-trione; tert-butyl(dihydroxy)[ ]trione; C15H18O8; Bilobalide;; Bilobalide A;; ( )-Bilobalide; AC1L2K4G; MLS000563448

Indication

Disease Entry	ICD 11	Status	REF
Discovery agent	N.A.	Investigative	[1]

• Cross-matching ID:
  PubChem CID: 73581
  ChEBI ID: CHEBI:3103
  CAS Number: CAS 33570-04-6
  TTD Drug ID: DM09Z35

Molecule-Related Drug Atlas

Drug(s) Targeting Glycine receptor (GlyR)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
THIOCOLCHICOSIDE	DMEPWYA	Muscle spasm	MB47.3	Approved	[5]
ZD-9379	DM3KYO4	Cerebrovascular ischaemia	8B1Z	Phase 1	[6]
UK-240455	DMSCXB7	Nerve injury	ND56.4	Phase 1	[7]
MDL-27531	DMC60S8	Epilepsy	8A60-8A68	Phase 1	[8]
Gavestinel	DM8IL1U	Nerve injury	ND56.4	Discontinued in Phase 2	[9]
GV-196771	DMFN21T	Migraine	8A80	Discontinued in Phase 2	[10]
GW 468816	DMQ92WF	Tobacco dependence	6C4A.2	Discontinued in Phase 2	[11]
M-241247	DMIY51U	Cerebrovascular ischaemia	8B1Z	Terminated	[12]
GINKOLIDE B	DMLIM7B	Sepsis	1G40-1G41	Terminated	[13]
3-demethoxy-3-D-lyxopyranosylaminothiocolchicine	DME8VPC	Discovery agent	N.A.	Investigative	[5]

Drug(s) Targeting 5-HT 3B receptor (HTR3B)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
BEMESETRON	DMSPJX9	N. A.	N. A.	Discontinued in Phase 3	[14]
SEROTONIN	DMOFCRY	Discovery agent	N.A.	Investigative	[15]
2-methyl-5-HT	DM1S5CB	N. A.	N. A.	Investigative	[16]
QUIPAZINE	DMPY6IG	Discovery agent	N.A.	Investigative	[15]
MESULERGINE	DMKGWAH	Discovery agent	N.A.	Investigative	[17]
2-(4-Methyl-piperazin-1-yl)-quinoline	DMB8OY6	Discovery agent	N.A.	Investigative	[15]
BRL-24682	DMSB4EW	Discovery agent	N.A.	Investigative	[18]
6-(4-Methyl-piperazin-1-yl)-phenanthridine	DM1HAWR	Discovery agent	N.A.	Investigative	[15]
trichloroethanol	DMNALMF	Discovery agent	N.A.	Investigative	[19]
1-phenylbiguanide	DMA4XGL	Discovery agent	N.A.	Investigative	[20]

Drug(s) Targeting 5-HT 3A receptor (HTR3A)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Dolasetron	DMMG26Z	Nausea	MD90	Approved	[21]
Alosetron	DML2A03	Diarrhea-predominant irritable bowel syndrome	DD91.01	Approved	[22]
Tropisetron	DMNSJ7V	Fibromyalgia	MG30.01	Approved	[23]
Palonosetron	DMBHMOX	Nausea	MD90	Approved	[24]
Levetiracetam	DMTGDN8	Epilepsy	8A60-8A68	Approved	[23]
Procaine	DM4LSNE	Anaesthesia	9A78.6	Approved	[25]
Cilansetron	DMP0NGX	Irritable bowel syndrome	DD91.0	Phase 3	[26]
BEMESETRON	DMSPJX9	N. A.	N. A.	Discontinued in Phase 3	[14]
Norcisapride	DMJSKUI	Gastroesophageal reflux disease	DA22.Z	Discontinued in Phase 2	[27]
YM-114	DML2IXO	Nausea	MD90	Discontinued in Phase 2	[28]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
5-HT 3A receptor (HTR3A)	TTPC4TU	5HT3A_HUMAN	Blocker (channel blocker)	[2]
5-HT 3B receptor (HTR3B)	TTR6K75	5HT3B_HUMAN	Blocker (channel blocker)	[3]
Glycine receptor (GlyR)	TTZ8EM9	GLRA1_HUMAN; GLRA2_HUMAN; GLRA3_HUMAN; GLRA4_HUMAN; GLRB_HUMAN	Antagonist	[4]

References

• [1] 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: 2366).
• [2] Binding sites for bilobalide, diltiazem, ginkgolide, and picrotoxinin at the 5-HT3 receptor. Mol Pharmacol. 2011 Jul;80(1):183-90.
• [3] Ginkgolide B and bilobalide block the pore of the 5-HT eceptor at a location that overlaps the picrotoxin binding site. Neuropharmacology. 2011 Feb-Mar;60(2-3):488-95.
• [4] 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. (Target id: 427).
• [5] 3-demethoxy-3-glycosylaminothiocolchicines: Synthesis of a new class of putative muscle relaxant compounds. J Med Chem. 2006 Sep 7;49(18):5571-7.
• [6] Neuroprotective potential of ionotropic glutamate receptor antagonists. Neurotox Res. 2002 Mar;4(2):119-26.
• [7] UK-315716/UK-240455. Pfizer. Curr Opin Investig Drugs. 2001 Dec;2(12):1737-9.
• [8] MDL 27,531 reduces spontaneous hindlimb contractions in rats with chronic transections of the spinal cord. Neurosci Lett. 1992 Nov 23;147(1):101-5.
• [9] Glycine antagonist (gavestinel) in neuroprotection (GAIN International) in patients with acute stroke: a randomised controlled trial.GAIN International Investigators.Lancet.2000 Jun 3;355(9219):1949-54.
• [10] First time in human for GV196771: interspecies scaling applied on dose selection. J Clin Pharmacol. 1999 Jun;39(6):560-6.
• [11] A double-blind, placebo-controlled trial of the NMDA glycine site antagonist, GW468816, for prevention of relapse to smoking in females.J Clin Psychopharmacol.2011 Oct;31(5):597-602.
• [12] Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800003415)
• [13] Probing the pharmacophore of ginkgolides as glycine receptor antagonists. J Med Chem. 2007 Apr 5;50(7):1610-7.
• [14] Zatosetron, a potent, selective, and long-acting 5HT3 receptor antagonist: synthesis and structure-activity relationships. J Med Chem. 1992 Jan 24;35(2):310-9.
• [15] Novel potent and selective central 5-HT3 receptor ligands provided with different intrinsic efficacy. 2. Molecular basis of the intrinsic efficacy ... J Med Chem. 1999 May 6;42(9):1556-75.
• [16] The 5-HT3B subunit is a major determinant of serotonin-receptor function. Nature. 1999 Jan 28;397(6717):359-63.
• [17] Novel and highly potent 5-HT3 receptor agonists based on a pyrroloquinoxaline structure. J Med Chem. 1997 Oct 24;40(22):3670-8.
• [18] Synthesis and structure-affinity relationships of novel N-(1-ethyl-4-methylhexahydro-1,4-diazepin-6-yl)pyridine-3-carboxamides with potent serotoni... J Med Chem. 2003 Feb 27;46(5):702-15.
• [19] Co-expression of the 5-HT(3B) subunit with the 5-HT(3A) receptor reduces alcohol sensitivity. Brain Res Mol Brain Res. 2005 Dec 14;142(2):146-50.
• [20] Pharmacological comparison of human homomeric 5-HT3A receptors versus heteromeric 5-HT3A/3B receptors. Neuropharmacology. 2001 Aug;41(2):282-4.
• [21] Palonosetron plus dexamethasone versus granisetron plus dexamethasone for prevention of nausea and vomiting during chemotherapy: a double-blind, do... Lancet Oncol. 2009 Feb;10(2):115-24.
• [22] Efficacy of 5-HT3 antagonists and 5-HT4 agonists in irritable bowel syndrome: systematic review and meta-analysis. Am J Gastroenterol. 2009 Jul;104(7):1831-43; quiz 1844.
• [23] Emerging therapies for fibromyalgia. Expert Opin Emerg Drugs. 2008 Mar;13(1):53-62.
• [24] Management of postoperative nausea and vomiting: focus on palonosetron. Ther Clin Risk Manag. 2009 Feb;5(1):21-34.
• [25] Local anesthetics have different mechanisms and sites of action at recombinant 5-HT3 receptors. Reg Anesth Pain Med. 2007 Nov-Dec;32(6):462-70.
• [26] Cilansetron: a new serotonergic agent for the irritable bowel syndrome with diarrhoea.Expert Opin Investig Drugs.2005 Feb;14(2):185-93.
• [27] mu-Opioid/5-HT4 dual pharmacologically active agents-efforts towards an effective opioid analgesic with less GI and respiratory side effects (Part I). Bioorg Med Chem Lett. 2009 Oct 1;19(19):5679-83.
• [28] Effect of serotonin (5-HT)3-receptor antagonists YM060, YM114 (KAE-393), ondansetron and granisetron on 5-HT4 receptors and gastric emptying in rodents. Jpn J Pharmacol. 1995 Nov;69(3):205-14.