rasagiline Indications/Contra | FAERs-F | FAERs-M | Orange Bk | BioActivity |

Stem definition	Drug id	CAS RN
monoamine oxydase (MAO)-inhibitors type B	3521	136236-51-6

Description:

Molecule	Description
Molfile Inchi Smiles Synonyms: TVP-1022 rasagiline hydrochloride rasagiline azilect (R)-(+)-Rasagiline rasagiline mesylate TV-1030 rasagiline mesilate	Rasagiline is a selective, irreversible MAO-B inhibitor indicated for the treatment of idiopathic Parkinson's disease. The results of a clinical trial designed to examine the effects of rasagiline tablets on blood pressure when it is administered with increasing doses of tyramine indicates the functional selectivity can be incomplete when healthy subjects ingest large amounts of tyramine while receiving recommended doses of rasagiline tablets. The selectivity for inhibiting MAO-B diminishes in a dose-related manner. One mechanism is believed to be related to its MAO-B inhibitory activity, which causes an increase in extracellular levels of dopamine in the striatum. The elevated dopamine level and subsequent increased dopaminergic activity are likely to mediate rasagiline’s beneficial effects seen in models of dopaminergic motor dysfunction. Molecular weight: 171.24 Formula: C12H13N CLOGP: 2.34 LIPINSKI: 0 HAC: 1 HDO: 1 TPSA: 12.03 ALOGS: -3.84 ROTB: 2 Status: OFP Legend: OFP - off patent OFM - off market ONP - on patent

Molecule

Description

Molfile Inchi Smiles

Synonyms:

TVP-1022
rasagiline hydrochloride
rasagiline
azilect
(R)-(+)-Rasagiline
rasagiline mesylate
TV-1030
rasagiline mesilate

Rasagiline is a selective, irreversible MAO-B inhibitor indicated for the treatment of idiopathic Parkinson's disease. The results of a clinical trial designed to examine the effects of rasagiline tablets on blood pressure when it is administered with increasing doses of tyramine indicates the functional selectivity can be incomplete when healthy subjects ingest large amounts of tyramine while receiving recommended doses of rasagiline tablets. The selectivity for inhibiting MAO-B diminishes in a dose-related manner. One mechanism is believed to be related to its MAO-B inhibitory activity, which causes an increase in extracellular levels of dopamine in the striatum. The elevated dopamine level and subsequent increased dopaminergic activity are likely to mediate rasagiline’s beneficial effects seen in models of dopaminergic motor dysfunction.

Molecular weight: 171.24
Formula: C12H13N
CLOGP: 2.34
LIPINSKI: 0
HAC: 1
HDO: 1
TPSA: 12.03
ALOGS: -3.84
ROTB: 2

Status: OFP

Legend:
OFP - off patent
OFM - off market
ONP - on patent

Drug dosage:

Dose	Unit	Route
1	mg	O

ADMET properties:

Property	Value	Reference
BA (Bioavailability)	36 %	Kim MT, Sedykh A, Chakravarti SK, Saiakhov RD, Zhu H

Approvals:

Date	Agency	Company	Orphan
May 16, 2006	FDA	TEVA
March 23, 2018	PMDA	Takeda Pharmaceutical Company Limited

FDA Adverse Event Reporting System (Female)

MedDRA adverse event term	Likelihood ratio	Likelihood ratio threshold	Patients taking drug having adverse event	Patients taking drug not having adverse event	Patients not taking drug having adverse event	Patients not taking drug not having adverse event
Hallucination	214.83	23.18	101	4542	53737	53290686
Dyskinesia	192.46	23.18	80	4563	31753	53312670
Hallucination, visual	176.30	23.18	65	4578	18767	53325656
Serotonin syndrome	125.43	23.18	56	4587	26350	53318073
Fall	113.54	23.18	147	4496	358293	52986130
Delusion	71.85	23.18	30	4613	11979	53332444
Pleurothotonus	67.36	23.18	17	4626	1362	53343061
On and off phenomenon	65.60	23.18	19	4624	2559	53341864
Drug interaction	60.01	23.18	84	4559	219245	53125178
Tremor	53.30	23.18	60	4583	125676	53218747
Confusional state	52.52	23.18	74	4569	194147	53150276
Orthostatic hypotension	51.14	23.18	32	4611	29721	53314702
Bradykinesia	48.07	23.18	17	4626	4336	53340087
Gambling disorder	47.85	23.18	13	4630	1387	53343036
Freezing phenomenon	45.60	23.18	13	4630	1654	53342769
Compulsive shopping	44.42	23.18	11	4632	815	53343608
Sudden onset of sleep	41.47	23.18	10	4633	663	53343760
Impulse-control disorder	39.45	23.18	10	4633	815	53343608
Hypersexuality	38.83	23.18	9	4634	503	53343920
Muscle rigidity	36.05	23.18	18	4625	10823	53333600
Coronary artery dissection	34.68	23.18	9	4634	805	53343618
Labelled drug-drug interaction medication error	33.04	23.18	17	4626	10882	53333541
Altered state of consciousness	31.25	23.18	22	4621	24814	53319609
Choking	29.66	23.18	15	4628	9261	53335162
Stoma site extravasation	29.65	23.18	7	4636	424	53343999
Serum serotonin increased	28.99	23.18	6	4637	197	53344226
Gait disturbance	28.25	23.18	50	4593	158792	53185631
Compulsive hoarding	27.65	23.18	5	4638	79	53344344
Psychotic symptom	27.63	23.18	8	4635	1075	53343348
Fracture	25.11	23.18	17	4626	18002	53326421
Dystonia	24.90	23.18	15	4628	13006	53331417
Dementia	23.81	23.18	16	4627	16734	53327689
Parkinsonian gait	23.65	23.18	6	4637	490	53343933
Sleep talking	23.56	23.18	7	4636	1029	53343394
Nocturia	23.38	23.18	12	4631	7638	53336785

FDA Adverse Event Reporting System (Male)

MedDRA adverse event term	Likelihood ratio	Likelihood ratio threshold	Patients taking drug having adverse event	Patients taking drug not having adverse event	Patients not taking drug having adverse event	Patients not taking drug not having adverse event
Hallucination	456.21	24.50	228	7265	52391	32453642
Impulse-control disorder	279.15	24.50	66	7427	1483	32504550
Dyskinesia	239.08	24.50	114	7379	23489	32482544
Hypersexuality	213.96	24.50	54	7439	1603	32504430
Hallucination, visual	177.09	24.50	84	7409	17075	32488958
Gambling disorder	155.50	24.50	43	7450	1826	32504207
Fall	151.81	24.50	205	7288	195996	32310037
On and off phenomenon	117.05	24.50	40	7453	3461	32502572
Orthostatic hypotension	116.71	24.50	73	7420	25577	32480456
Confusional state	114.18	24.50	152	7341	142963	32363070
Dopamine dysregulation syndrome	113.01	24.50	26	7467	515	32505518
Freezing phenomenon	94.90	24.50	31	7462	2332	32503701
Delusion	90.69	24.50	49	7444	13059	32492974
Serotonin syndrome	73.58	24.50	49	7444	19068	32486965
Abnormal behaviour	72.21	24.50	55	7438	26411	32479622
Resting tremor	68.10	24.50	18	7475	642	32505391
Somnolence	64.49	24.50	98	7395	103699	32402334
Dystonia	60.62	24.50	35	7458	10588	32495445
Compulsive shopping	54.34	24.50	14	7479	451	32505582
Cogwheel rigidity	51.34	24.50	17	7476	1333	32504700
Bradykinesia	50.42	24.50	23	7470	4263	32501770
Tremor	49.39	24.50	76	7417	81201	32424832
Stereotypy	48.47	24.50	14	7479	696	32505337
Muscle rigidity	46.26	24.50	30	7463	11156	32494877
Balance disorder	44.43	24.50	50	7443	39409	32466624
Cognitive disorder	44.07	24.50	41	7452	25853	32480180
Sudden onset of sleep	44.04	24.50	12	7481	481	32505552
Supine hypertension	42.52	24.50	11	7482	360	32505673
Psychomotor hyperactivity	41.75	24.50	26	7467	9013	32497020
Marasmus	40.96	24.50	12	7481	627	32505406
Jealous delusion	40.68	24.50	10	7483	265	32505768
Akinesia	40.28	24.50	17	7476	2616	32503417
Stoma site discharge	38.27	24.50	15	7478	1910	32504123
Oesophageal achalasia	37.42	24.50	10	7483	372	32505661
Anticholinergic syndrome	36.91	24.50	12	7481	888	32505145
Obsessive-compulsive personality disorder	34.01	24.50	8	7485	175	32505858
Sleep disorder	33.75	24.50	36	7457	26716	32479317
Paraphilia	33.25	24.50	7	7486	90	32505943
Gait disturbance	32.76	24.50	63	7430	80345	32425688
Parkinson's disease	32.74	24.50	13	7480	1713	32504320
Dementia	32.54	24.50	26	7467	13360	32492673
Agitation	31.26	24.50	51	7442	57185	32448848
Mesenteric artery thrombosis	31.10	24.50	9	7484	450	32505583
Autonomic nervous system imbalance	30.94	24.50	14	7479	2546	32503487
Psychotic disorder	30.86	24.50	32	7461	22988	32483045
Hyperkinesia	29.24	24.50	13	7480	2269	32503764
Restlessness	28.80	24.50	32	7461	24849	32481184
Hyperthermia	28.59	24.50	22	7471	10706	32495327
Stoma site erythema	28.15	24.50	11	7482	1389	32504644
Blood lactic acid	27.84	24.50	8	7485	390	32505643
Thunderclap headache	27.70	24.50	6	7487	89	32505944
Dysphagia	27.31	24.50	50	7443	61426	32444607
Binge eating	27.22	24.50	6	7487	97	32505936
Therapeutic product effect variable	27.04	24.50	12	7481	2084	32503949
Prescribed underdose	25.83	24.50	19	7474	8640	32497393
Aggression	25.54	24.50	38	7455	39351	32466682
Fracture	25.39	24.50	17	7476	6662	32499371
Disturbance in attention	24.86	24.50	29	7464	23724	32482309
Obsessive-compulsive disorder	24.84	24.50	15	7478	4919	32501114
Nocturia	24.63	24.50	19	7474	9275	32496758

Pharmacologic Action:

Source	Code	Description
ATC	N04BD02	NERVOUS SYSTEM ANTI-PARKINSON DRUGS DOPAMINERGIC AGENTS Monoamine oxidase B inhibitors
FDA MoA	N0000000184	Monoamine Oxidase Inhibitors
MeSH PA	D002491	Central Nervous System Agents
MeSH PA	D004791	Enzyme Inhibitors
MeSH PA	D008996	Monoamine Oxidase Inhibitors
MeSH PA	D018696	Neuroprotective Agents
MeSH PA	D020011	Protective Agents
FDA EPC	N0000175744	Monoamine Oxidase Inhibitor
CHEBI has role	CHEBI:38623	monoamine oxidase inhibitors
CHEBI has role	CHEBI:63726	neuroprotective agents

Drug Use (View source of the data)

Disease	Relation	SNOMED_ID	DOID
Parkinson's disease	indication	49049000	DOID:14330
Dyskinesia	contraindication	9748009
Bipolar disorder	contraindication	13746004	DOID:3312
Orthostatic hypotension	contraindication	28651003
Hypertensive disorder	contraindication	38341003	DOID:10763
Epilepsy	contraindication	84757009	DOID:1826
Disease of liver	contraindication	235856003	DOID:409
Pheochromocytoma	contraindication	302835009
Malignant melanoma	contraindication	372244006

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation level	Dissociation constant	Type (acidic/basic)
pKa1	7.54	Basic

Orange Book patent data (new drug applications)

Formulation strength	Trade name	Applicant	Application number	Approval date	Type	Dose form	Route	Patent number	Patent expiration date	Patent use
EQ 0.5MG BASE	AZILECT	TEVA	N021641	May 16, 2006	RX	TABLET	ORAL	7815942	Aug. 27, 2027	TREATMENT OF PARKINSONS DISEASE
EQ 1MG BASE	AZILECT	TEVA	N021641	May 16, 2006	RX	TABLET	ORAL	7815942	Aug. 27, 2027	TREATMENT OF PARKINSONS DISEASE

Orange Book exclusivity data (new drug applications)

None

Bioactivity Summary:

Target	Class	Pharos	UniProt	Action	Type	Activity value (-log[M])	Bioact source	MoA source
Amine oxidase [flavin-containing] B	Enzyme	P27338	AOFB_HUMAN	INHIBITOR	Ki	6.15	CHEMBL	CHEMBL
Acetylcholinesterase	Enzyme	P22303	ACES_HUMAN		IC50	7.72	CHEMBL
Cholinesterase	Enzyme	P06276	CHLE_HUMAN		IC50	5.32	CHEMBL
Amine oxidase [flavin-containing] A	Enzyme	P21397	AOFA_HUMAN		Ki	5.01	CHEMBL
Amine oxidase [flavin-containing] B	Enzyme		AOFB_RAT		IC50	8.36	CHEMBL
Amine oxidase [flavin-containing] A	Enzyme		AOFA_RAT		IC50	6.39	CHEMBL

External reference:

ID	Source
4025261	VUID
N0000179514	NUI
D02562	KEGG_DRUG
136236-50-5	SECONDARY_CAS_RN
4025261	VANDF
4025262	VANDF
C0525678	UMLSCUI
CHEBI:63620	CHEBI
RAU	PDB_CHEM_ID
CHEMBL887	ChEMBL_ID
DB01367	DRUGBANK_ID
CHEMBL1201142	ChEMBL_ID
CHEMBL1235738	ChEMBL_ID
3052776	PUBCHEM_CID
7151	INN_ID
C031967	MESH_SUPPLEMENTAL_RECORD_UI
6641	IUPHAR_LIGAND_ID
003N66TS6T	UNII
134748	RXNORM
162358	MMSL
20417	MMSL
70623	MMSL
d05612	MMSL
010775	NDDF
010776	NDDF
418734001	SNOMEDCT_US
419010007	SNOMEDCT_US
734664007	SNOMEDCT_US

Pharmaceutical products:

Product	Category	Ingredients	NDC	Form	Quantity	Route	Marketing	Label
Rasagiline	HUMAN PRESCRIPTION DRUG LABEL	1	0093-3060	TABLET	0.50 mg	ORAL	NDA authorized generic	29 sections
Rasagiline	HUMAN PRESCRIPTION DRUG LABEL	1	0093-3061	TABLET	1 mg	ORAL	NDA authorized generic	29 sections
Rasagiline Mesylate	HUMAN PRESCRIPTION DRUG LABEL	1	0378-1270	TABLET	0.50 mg	ORAL	ANDA	30 sections
Rasagiline Mesylate	HUMAN PRESCRIPTION DRUG LABEL	1	0378-1271	TABLET	1 mg	ORAL	ANDA	30 sections
Rasagiline	Human Prescription Drug Label	1	16714-770	TABLET	0.50 mg	ORAL	ANDA	29 sections
Rasagiline	Human Prescription Drug Label	1	16714-771	TABLET	1 mg	ORAL	ANDA	29 sections
Rasagiline Mesylate	Human Prescription Drug Label	1	23155-746	TABLET	0.50 mg	ORAL	ANDA	29 sections
Rasagiline Mesylate	Human Prescription Drug Label	1	23155-747	TABLET	1 mg	ORAL	ANDA	29 sections
Rasagiline	HUMAN PRESCRIPTION DRUG LABEL	1	42291-779	TABLET	0.50 mg	ORAL	NDA authorized generic	29 sections
Rasagiline	HUMAN PRESCRIPTION DRUG LABEL	1	42291-780	TABLET	1 mg	ORAL	NDA authorized generic	29 sections
RASAGILINE	HUMAN PRESCRIPTION DRUG LABEL	1	42571-220	TABLET	0.50 mg	ORAL	ANDA	29 sections
RASAGILINE	HUMAN PRESCRIPTION DRUG LABEL	1	42571-221	TABLET	1 mg	ORAL	ANDA	29 sections
Azilect	HUMAN PRESCRIPTION DRUG LABEL	1	43353-015	TABLET	1 mg	ORAL	NDA	30 sections
Rasagiline	HUMAN PRESCRIPTION DRUG LABEL	1	47781-683	TABLET	0.50 mg	ORAL	ANDA	27 sections
Rasagiline	HUMAN PRESCRIPTION DRUG LABEL	1	47781-690	TABLET	1 mg	ORAL	ANDA	27 sections
Azilect	HUMAN PRESCRIPTION DRUG LABEL	1	54868-6206	TABLET	1 mg	ORAL	NDA	30 sections
Rasagiline	Human Prescription Drug Label	1	67877-259	TABLET	0.50 mg	ORAL	ANDA	29 sections
Rasagiline	Human Prescription Drug Label	1	67877-260	TABLET	1 mg	ORAL	ANDA	29 sections
Azilect	HUMAN PRESCRIPTION DRUG LABEL	1	68546-142	TABLET	0.50 mg	ORAL	NDA	30 sections
Azilect	HUMAN PRESCRIPTION DRUG LABEL	1	68546-229	TABLET	1 mg	ORAL	NDA	30 sections