Details of the Drug

General Information of Drug (ID: DM5SQ1G)

Drug Name

Dihydroergocristine

Synonyms

Nehydrin

Indication

Disease Entry	ICD 11	Status	REF
Alcohol dependence	6C40.2	Approved	[1]
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Drug Type

Small molecular drug

Structure

3D MOL

2D MOL

#Ro5 Violations (Lipinski): 1

Molecular Weight (mw)

611.7

Logarithm of the Partition Coefficient (xlogp)

3.3

Rotatable Bond Count (rotbonds)

Hydrogen Bond Donor Count (hbonddonor)

Hydrogen Bond Acceptor Count (hbondacc)

ADMET Property

Absorption AUC: The area under the plot of plasma concentration (AUC) of drug is 0.39 mcgh/L [2]
Absorption Cmax: The maximum plasma concentration (Cmax) of drug is 0.28 mcg/L [2]
Absorption Tmax: The time to maximum plasma concentration (Tmax) is 0.46 h [2]
Clearance: The sytemic clearance of drug is 2.65 L/h/kg [3]
Elimination: The most important elimination route of dihydroergocristine is in via the bile and it accounts for over 85% of the eliminated dose [4]
Metabolism: The drug is metabolized via the liver [2]
Vd: The volume of distribution (Vd) of drug is 52 L/kg [3]

Chemical Identifiers

Formula: C35H41N5O5
IUPAC Name: (6aR,9R,10aR)-N-[(1S,2S,4R,7S)-7-benzyl-2-hydroxy-5,8-dioxo-4-propan-2-yl-3-oxa-6,9-diazatricyclo[7.3.0.02,6]dodecan-4-yl]-7-methyl-6,6a,8,9,10,10a-hexahydro-4H-indolo[4,3-fg]quinoline-9-carboxamide
Canonical SMILES: CC(C)[C@@]1(C(=O)N2[C@H](C(=O)N3CCC[C@H]3[C@@]2(O1)O)CC4=CC=CC=C4)NC(=O)[C@@H]5C[C@H]6[C@@H](CC7=CNC8=CC=CC6=C78)N(C5)C
InChI: InChI=1S/C35H41N5O5/c1-20(2)34(37-31(41)23-16-25-24-11-7-12-26-30(24)22(18-36-26)17-27(25)38(3)19-23)33(43)40-28(15-21-9-5-4-6-10-21)32(42)39-14-8-13-29(39)35(40,44)45-34/h4-7,9-12,18,20,23,25,27-29,36,44H,8,13-17,19H2,1-3H3,(H,37,41)/t23-,25-,27-,28+,29+,34-,35+/m1/s1
InChIKey: DEQITUUQPICUMR-HJPBWRTMSA-N

Cross-matching ID

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Adrenergic receptor alpha-2C (ADRA2C)	TT2NUT5	ADA2C_HUMAN	Modulator	[5]

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Drug Transporter (DTP)

Molecular Interaction Atlas (MIA)

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Molecular Expression Atlas of This Drug

The Studied Disease

Alcohol dependence

ICD Disease Classification

6C40.2

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Adrenergic receptor alpha-2C (ADRA2C)	DTT	ADRA2C	1.76E-01	-0.06	-0.28
P-glycoprotein 1 (ABCB1)	DTP	P-GP	9.39E-02	1.07E-01	2.80E-01

Molecular Expression Atlas (MEA)

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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: 278).
2	Longoria TC, Tewari KS: Evaluation of the pharmacokinetics and metabolism of pembrolizumab in the treatment of melanoma. Expert Opin Drug Metab Toxicol. 2016 Oct;12(10):1247-53. doi: 10.1080/17425255.2016.1216976. Epub 2016 Aug 16.
3	Grognet JM, Riviere R, Istin M, Zanotti A, Coppi G: [The pharmacokinetics of dihydroergocristine after intravenous and oral administration in rats]. Arzneimittelforschung. 1992 Nov;42(11A):1394-6.
4	Nimmerfall F, Rosenthaler J: Ergot alkaloids: hepatic distribution and estimation of absorption by measurement of total radioactivity in bile and urine. J Pharmacokinet Biopharm. 1976 Feb;4(1):57-66.
5	Effect of dihydroergocristine on blood pressure and activity at peripheral alpha-adrenoceptors in pithed rats. Eur J Pharmacol. 1984 Jan 13;97(1-2):21-7.
6	Interaction of cytochrome P450 3A inhibitors with P-glycoprotein. J Pharmacol Exp Ther. 2002 Oct;303(1):323-32.