Target Information

Target General Information

Top

Target ID

T64765 (Former ID: TTDC00079)

Target Name

Histamine H3 receptor (H3R)

Synonyms

Histamine receptor 3; HH3R; GPCR97; G-protein coupled receptor 97; G protein-coupled receptor 97

Gene Name

HRH3

Target Type

Successful target

[1]

Disease

[+] 1 Target-related Diseases

Somnolence [ICD-11: MG42]

Function

Signals through the inhibition of adenylate cyclase and displays high constitutive activity (spontaneous activity in the absence of agonist). Agonist stimulation of isoform 3 neither modified adenylate cyclase activity nor induced intracellular calcium mobilization. The H3 subclass of histamine receptors could mediate the histamine signals in CNS and peripheral nervous system.

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BioChemical Class

GPCR rhodopsin

UniProt ID

HRH3_HUMAN

Sequence

MERAPPDGPLNASGALAGEAAAAGGARGFSAAWTAVLAALMALLIVATVLGNALVMLAFV
ADSSLRTQNNFFLLNLAISDFLVGAFCIPLYVPYVLTGRWTFGRGLCKLWLVVDYLLCTS
SAFNIVLISYDRFLSVTRAVSYRAQQGDTRRAVRKMLLVWVLAFLLYGPAILSWEYLSGG
SSIPEGHCYAEFFYNWYFLITASTLEFFTPFLSVTFFNLSIYLNIQRRTRLRLDGAREAA
GPEPPPEAQPSPPPPPGCWGCWQKGHGEAMPLHRYGVGEAAVGAEAGEATLGGGGGGGSV
ASPTSSSGSSSRGTERPRSLKRGSKPSASSASLEKRMKMVSQSFTQRFRLSRDRKVAKSL
AVIVSIFGLCWAPYTLLMIIRAACHGHCVPDYWYETSFWLLWANSAVNPVLYPLCHHSFR
RAFTKLLCPQKLKIQPHSSLEHCWK

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3D Structure

Click to Show 3D Structure of This Target

AlphaFold

HIT2.0 ID

T88AHJ

Drugs and Modes of Action

Top

Approved Drug(s)

[+] 1 Approved Drugs

Pitolisant

Drug Info

Approved

Excessive daytime sleepiness

[2]

Clinical Trial Drug(s)

[+] 17 Clinical Trial Drugs

SUVN-G3031

Drug Info

Phase 3

Cognitive impairment

[3], [4]

ABT-288

Drug Info

Phase 2

Alzheimer disease

[5], [6]

ABT-652

Drug Info

Phase 2

Musculoskeletal pain

[7]

AZD-5213

Drug Info

Phase 2

Alzheimer disease

[8]

Bavisant

Drug Info

Phase 2

Attention deficit hyperactivity disorder

[9]

GSK239512

Drug Info

Phase 2

Dementia

[10]

JNJ-17216498

Drug Info

Phase 2

Narcolepsy

[11]

JNJ-39220675

Drug Info

Phase 2

Alcohol dependence

[12]

S-38093

Drug Info

Phase 2

Alzheimer disease

[13]

SAR-110894

Drug Info

Phase 2

Alzheimer disease

[14]

ABT-239

Drug Info

Phase 1

Cognitive impairment

[15], [16]

APD-916

Drug Info

Phase 1

Sleep-wake disorder

[17]

HPP404

Drug Info

Phase 1

Allergic rhinitis

[18]

Irdabisant

Drug Info

Phase 1

Cognitive impairment

[19]

MK-3134

Drug Info

Phase 1

Dementia

[20]

MK-7288

Drug Info

Phase 1

Excessive daytime sleepiness

[21]

MK-0249

Drug Info

Clinical trial

Insulin-resistant disorder

[22]

Patented Agent(s)

[+] 9 Patented Agents

Biphenyl derivative 4

Drug Info

Patented

Histamine H3-associated disorder

[23]

Phenylsulfonyl derivative 1

Drug Info

Patented

Central nervous system disease

[23]

Phenylsulfonyl derivative 2

Drug Info

Patented

Central nervous system disease

[23]

Phenylsulfonyl derivative 3

Drug Info

Patented

Central nervous system disease

[23]

Phenylsulfonyl derivative 4

Drug Info

Patented

Central nervous system disease

[23]

PMID29334795-Compound-21

Drug Info

Patented

Progressive supranuclear palsy

[23]

PMID29334795-Compound-22

Drug Info

Patented

Neuropathic pain

[23]

PMID29334795-Compound-23

Drug Info

Patented

Schizophrenia

[23]

PMID29334795-Compound-28

Drug Info

Patented

Histamine H3-associated disorder

[23]

Discontinued Drug(s)

[+] 9 Discontinued Drugs

BP-2.94

Drug Info

Discontinued in Phase 2

Pain

[24]

Cipralisant

Drug Info

Discontinued in Phase 2

Attention deficit hyperactivity disorder

[25], [26]

GSK835726

Drug Info

Discontinued in Phase 2

Allergic rhinitis

[27]

GSK1004723

Drug Info

Discontinued in Phase 1

Allergic rhinitis

[28]

SAR-152954

Drug Info

Discontinued in Phase 1

Sleep-wake disorder

[29]

GT-2016

Drug Info

Terminated

Alzheimer disease

[30]

GT-2203

Drug Info

Terminated

Anxiety disorder

[31]

Thioperamide

Drug Info

Terminated

Cognitive impairment

[32], [33]

UCL-1390

Drug Info

Terminated

Pain

[34]

Mode of Action

[+] 8 Modes of Action

Agonist

[+] 19 Agonist drugs

Pitolisant

Drug Info

[2]

MK-3134

Drug Info

[47]

MK-7288

Drug Info

[48]

MK-0249

Drug Info

[49]

GT-2203

Drug Info

[54]

(R)-alpha-methylhistamine

Drug Info

[16], [61], [62]

(S)-alpha-methylhistamine

Drug Info

[63]

imbutamine

Drug Info

[86]

Imetit

Drug Info

[16]

Immepip

Drug Info

[16]

Immethridine

Drug Info

[16]

impentamine

Drug Info

[86]

impromidine

Drug Info

[62]

Methimepip

Drug Info

[16]

N-methylhistamine

Drug Info

[62]

N-[3H]alpha-methylhistamine

Drug Info

[89]

N-[3H]methylhistamine

Drug Info

[62]

VUF 5207

Drug Info

[90]

VUF 8328

Drug Info

[90]

Antagonist

[+] 43 Antagonist drugs

SUVN-G3031

Drug Info

[3], [4]

AZD-5213

Drug Info

[37]

Bavisant

Drug Info

[38]

GSK239512

Drug Info

[39]

JNJ-17216498

Drug Info

[40]

JNJ-39220675

Drug Info

[41]

S-38093

Drug Info

[42]

SAR-110894

Drug Info

[37]

ABT-239

Drug Info

[16], [43], [44]

APD-916

Drug Info

[45]

HPP404

Drug Info

[18]

Irdabisant

Drug Info

[46]

GSK835726

Drug Info

[39]

GSK1004723

Drug Info

[39]

SAR-152954

Drug Info

[52]

Thioperamide

Drug Info

[16], [55]

UCL-1390

Drug Info

[26]

A-304121

Drug Info

[80]

A-317920

Drug Info

[16]

A-331440

Drug Info

[16]

ATH-90879

Drug Info

[54]

burimamide

Drug Info

[62]

Ciproxifan

Drug Info

[16]

Clobenpropit

Drug Info

[16], [55]

EVT-501

Drug Info

[54]

FUB 349

Drug Info

[85], [76]

FUB-130

Drug Info

[54]

GSK-334429

Drug Info

[54]

GSK189254A

Drug Info

[16]

GT2394

Drug Info

[63]

JB 98064

Drug Info

[63]

JNJ-5207852

Drug Info

[16]

PF-3900422

Drug Info

[54]

Proxyfan

Drug Info

[16]

SCH79687

Drug Info

[16]

SUVN-G1031

Drug Info

[54]

UCB-2892

Drug Info

[54]

UCL1972

Drug Info

[16]

VUF 4904

Drug Info

[90]

VUF 5681

Drug Info

[16]

VUF5391

Drug Info

[16]

[123I]iodoproxyfan

Drug Info

[85]

[125I]iodophenpropit

Drug Info

[92]

Modulator

[+] 3 Modulator drugs

ABT-288

Drug Info

[35]

ABT-652

Drug Info

[36]

BP-2.94

Drug Info

[50]

Inhibitor

[+] 118 Inhibitor drugs

Benzo[d]oxazol-2(3H)-one derivative 1

Drug Info

[23]

Benzo[d]oxazol-2(3H)-one derivative 2

Drug Info

[23]

Benzo[d]oxazol-2(3H)-one derivative 3

Drug Info

[23]

Phenylsulfonyl derivative 1

Drug Info

[23]

Phenylsulfonyl derivative 2

Drug Info

[23]

Phenylsulfonyl derivative 3

Drug Info

[23]

Phenylsulfonyl derivative 4

Drug Info

[23]

PMID29334795-Compound-62

Drug Info

[23]

PMID29334795-Compound-66

Drug Info

[23]

PMID29334795-Compound-67

Drug Info

[23]

GR-175737

Drug Info

[53]

GT-2016

Drug Info

[53]

(1H-indol-2-yl)(piperazin-1-yl)methanone

Drug Info

[56]

(1R,2R)-2-(1H-Imidazol-4-yl)-1-methyl-propylamine

Drug Info

[57]

(1R,2S)-2-(1H-Imidazol-4-yl)-1-methyl-propylamine

Drug Info

[57]

(1S,2S)-2-(1H-Imidazol-4-yl)-cyclopentylamine

Drug Info

[57]

(R)-1-(2-methoxyphenethyl)-2-methylpyrrolidine

Drug Info

[58]

(R)-1-(3-methoxyphenethyl)-2-methylpyrrolidine

Drug Info

[58]

(R)-1-(4-methoxyphenethyl)-2-methylpyrrolidine

Drug Info

[58]

(R)-1-(4-nitrophenethyl)-2-methylpyrrolidine

Drug Info

[58]

(R)-2-(2-(2-methylpyrrolidin-1-yl)ethyl)phenol

Drug Info

[58]

(R)-2-(2-(2-methylpyrrolidin-1-yl)ethyl)pyridine

Drug Info

[58]

(R)-2-methyl-1-(2-m-tolyl-ethyl)-pyrrolidine

Drug Info

[58]

(R)-2-methyl-1-(2-p-tolyl-ethyl)-pyrrolidine

Drug Info

[58]

(R)-3-(1H-imidazol-4-yl)propyl sec-butylcarbamate

Drug Info

[59]

(R)-3-(2-(2-methylpyrrolidin-1-yl)ethyl)pyridine

Drug Info

[58]

(R)-4-(2-(2-methylpyrrolidin-1-yl)ethyl)pyridine

Drug Info

[58]

(R)-6-(2-(2-methylpyrrolidin-1-yl)ethyl)quinoline

Drug Info

[60]

(S)-1-(2-methoxyphenethyl)-2-methylpyrrolidine

Drug Info

[58]

(S)-1-(3-methoxyphenethyl)-2-methylpyrrolidine

Drug Info

[58]

(S)-1-(4-methoxyphenethyl)-2-methylpyrrolidine

Drug Info

[58]

(S)-1-(4-nitrophenethyl)-2-methylpyrrolidine

Drug Info

[58]

(S)-2-(2-(2-methylpyrrolidin-1-yl)ethyl)phenol

Drug Info

[58]

(S)-2-(2-(2-methylpyrrolidin-1-yl)ethyl)pyridine

Drug Info

[58]

(S)-2-methyl-1-(2-m-tolyl-ethyl)-pyrrolidine

Drug Info

[58]

(S)-2-methyl-1-(2-p-tolyl-ethyl)-pyrrolidine

Drug Info

[58]

(S)-3-(1H-imidazol-4-yl)propyl sec-butylcarbamate

Drug Info

[59]

(S)-4-(2-(2-methylpyrrolidin-1-yl)ethyl)pyridine

Drug Info

[58]

1-(2-(naphthalen-2-yl)ethyl)pyrrolidine

Drug Info

[58]

1-(2-m-tolyl-ethyl)-pyrrolidine

Drug Info

[58]

1-(2-methoxyphenethyl)pyrrolidine

Drug Info

[58]

1-(2-p-tolyl-ethyl)-pyrrolidine

Drug Info

[58]

1-(3-(2-(3-methoxyphenoxy)ethoxy)propyl)azepane

Drug Info

[64]

1-(3-(3-phenylpropoxy)propyl)piperidine

Drug Info

[65]

1-(3-(4-(2-fluoroethyl)phenoxy)propyl)piperidine

Drug Info

[66]

1-(3-(4-(fluoromethyl)phenoxy)propyl)piperidine

Drug Info

[66]

1-(3-methoxyphenethyl)pyrrolidine

Drug Info

[58]

1-(4-(benzyloxy)phenethyl)pyrrolidine

Drug Info

[58]

1-(4-methoxyphenethyl)pyrrolidine

Drug Info

[58]

1-(4-nitrophenethyl)pyrrolidine

Drug Info

[58]

1-[2-(2,4,6-trimethyl-phenyl)-ethyl]-pyrrolidine

Drug Info

[58]

2-((1H-imidazol-4-yl)methyl)pyridine

Drug Info

[67]

2-((2-ethoxyphenoxy)methyl)-4-isopropylmorpholine

Drug Info

[68]

2-(1,4'-bipiperidin-1'-yl)thiazolo[4,5-b]pyridine

Drug Info

[69]

2-(1,4'-bipiperidin-1'-yl)thiazolo[4,5-c]pyridine

Drug Info

[69]

2-(2-(4-tert-Butylphenylthio)ethyl)-1H-imidazole

Drug Info

[67]

2-(2-(pyrrolidin-1-yl)ethyl)-1H-indole

Drug Info

[58]

2-(2-(pyrrolidin-1-yl)ethyl)phenol

Drug Info

[58]

2-(2-(pyrrolidin-1-yl)ethyl)pyridine

Drug Info

[58]

2-(3-Methyl-3H-imidazol-4-yl)-ethylamine

Drug Info

[53]

2-(4-Cyclopentyl-piperazin-1-yl)-quinoline

Drug Info

[70]

2-(4-Cyclopropyl-piperazin-1-yl)-quinoline

Drug Info

[70]

2-(4-Isopropyl-piperazin-1-yl)-quinoline

Drug Info

[70]

2-(4-Methyl-piperazin-1-yl)-quinoline

Drug Info

[70]

2-(4-Propyl-piperazin-1-yl)-quinoline

Drug Info

[70]

2-(ethoxycarbonyl)-1H-indole-5-carboxylic acid

Drug Info

[71]

2-[2-(1H-Imidazol-4-yl)-cyclopropyl]-ethylamine

Drug Info

[72]

2-[4-(1-Ethyl-propyl)-piperazin-1-yl]-quinoline

Drug Info

[70]

3-((1H-imidazol-4-yl)methyl)pyridine

Drug Info

[67]

4-((1H-imidazol-4-yl)methyl)-1-heptylpiperidine

Drug Info

[73]

4-((1H-Imidazol-4-yl)methyl)-1-phenylpiperidine

Drug Info

[74]

4-((2R,3S)-2-Methyl-pyrrolidin-3-yl)-1H-imidazole

Drug Info

[57]

4-((2S,3R)-2-Methyl-pyrrolidin-3-yl)-1H-imidazole

Drug Info

[57]

4-(2-(3,4-Dimethylphenylamino)ethyl)-1H-imidazole

Drug Info

[75]

4-(2-(3-tert-Butylphenylamino)ethyl)-1H-imidazole

Drug Info

[75]

4-(2-(4-Cyclohexylphenylamino)ethyl)-1H-imidazole

Drug Info

[75]

4-(2-(4-Methoxyphenylamino)ethyl)-1H-imidazole

Drug Info

[75]

4-(2-(4-Methylphenylamino)ethyl)-1H-imidazole

Drug Info

[75]

4-(2-(4-tert-Butylphenylamino)ethyl)-1H-imidazole

Drug Info

[75]

4-(2-(Cyclohexylamino)ethyl)-1H-imidazole

Drug Info

[75]

4-(2-(Phenylamino)ethyl)-1H-imidazole

Drug Info

[75]

4-(2-(pyrrolidin-1-yl)ethyl)pyridine

Drug Info

[58]

4-(3-Phenoxy-propyl)-1H-imidazole

Drug Info

[76]

4-(4-butylpiperidin-1-yl)-1-o-tolylbutan-1-one

Drug Info

[77]

4-(6-Cyclohexyl-hex-3-ynyl)-1H-imidazole

Drug Info

[53]

4-(6-Cyclopentyl-hex-3-ynyl)-1H-imidazole

Drug Info

[53]

4-(7,7-Dimethyl-oct-3-ynyl)-1H-imidazole

Drug Info

[53]

4-(7-Methyl-oct-3-ynyl)-1H-imidazole

Drug Info

[53]

4-(8-Phenyl-oct-3-ynyl)-1H-imidazole

Drug Info

[53]

4-Benzyl-1-[3-phenylpropoxy)propyl]piperidine

Drug Info

[65]

4-Butyl-1-[3-(phenylpropoxy)propyl]piperidine

Drug Info

[65]

4-Hept-3-ynyl-1H-imidazole

Drug Info

[53]

4-Hex-3-ynyl-1H-imidazole

Drug Info

[53]

4-isopropyl-2-(phenoxymethyl)morpholine

Drug Info

[68]

4-Propyl-1-[3-(phenylpropoxy)propyl]piperidine

Drug Info

[65]

4-[3-(4-Butyl-phenoxy)-propyl]-1H-imidazole

Drug Info

[78]

4-[3-(4-Ethynyl-phenoxy)-propyl]-1H-imidazole

Drug Info

[78]

4-[3-(4-Methoxy-phenoxy)-propyl]-1H-imidazole

Drug Info

[76]

5-(2-(pyrrolidin-1-yl)ethyl)isothiazole

Drug Info

[58]

100

5-ethyl-2-(2-(pyrrolidin-1-yl)ethyl)pyridine

Drug Info

[58]

101

5-methoxy-2-(2-(pyrrolidin-1-yl)ethyl)-1H-indole

Drug Info

[58]

102

5-phenyl-2-(4-(piperidin-1-yl)butyl)oxazole

Drug Info

[79]

103

Aerophobin-1

Drug Info

[81]

104

APLYSAMINE

Drug Info

[82]

105

C-[2-(1H-Imidazol-4-yl)-cyclopropyl]-methylamine

Drug Info

[72]

106

CARCININE

Drug Info

[82]

107

CONESSINE

Drug Info

[83]

108

Des-bromoaplysamine-1

Drug Info

[84]

109

IODOPROXYFAN

Drug Info

[76]

110

JNJ-28583867

Drug Info

[87]

111

N-benzyl-4-cyclopentylpiperazine-1-carboxamide

Drug Info

[88]

112

N-methyl-2-(pyridin-2-yl)ethanamine

Drug Info

[71]

113

ST-1025

Drug Info

[79]

114

ST-1093

Drug Info

[79]

115

UCL-2138

Drug Info

[66]

116

Verongamine

Drug Info

[81]

117

VUF-10214

Drug Info

[91]

118

VUF-5297

Drug Info

[72]

Ligand

[+] 9 Ligand drugs

Piperazine carbamate/urea derivative 1

Drug Info

[23]

Piperazine carbamate/urea derivative 2

Drug Info

[23]

Piperazine carbamate/urea derivative 3

Drug Info

[23]

Piperazine carbamate/urea derivative 4

Drug Info

[23]

Piperazine carbamate/urea derivative 5

Drug Info

[23]

Piperazine carbamate/urea derivative 6

Drug Info

[23]

Piperazine carbamate/urea derivative 7

Drug Info

[23]

Triazolo-benzodiazepine derivative 1

Drug Info

[23]

Triazolo-benzodiazepine derivative 2

Drug Info

[23]

Agonis; Inverse agonist

[+] 1 Agonis; Inverse agonist drugs

PMID29334795-Compound-22

Drug Info

[23]

Inverse agonist

[+] 4 Inverse agonist drugs

PMID29334795-Compound-23

Drug Info

[23]

PMID29334795-Compound-24

Drug Info

[23]

PMID29334795-Compound-25

Drug Info

[23]

Pyridazin-3(2H)-one derivative 1

Drug Info

[23]

Binder

[+] 1 Binder drugs

Cipralisant

Drug Info

[51]

Chemical Structure based Activity Landscape of Target

Top

Drug Property Profile of Target

Top

(1) Molecular Weight (mw) based Drug Clustering

(2) Octanol/Water Partition Coefficient (xlogp) based Drug Clustering

(3) Hydrogen Bond Donor Count (hbonddonor) based Drug Clustering

(4) Hydrogen Bond Acceptor Count (hbondacc) based Drug Clustering

(5) Rotatable Bond Count (rotbonds) based Drug Clustering

(6) Topological Polar Surface Area (polararea) based Drug Clustering

"RO5" indicates the cutoff set by lipinski's rule of five; "D123AB" colored in GREEN denotes the no violation of any cutoff in lipinski's rule of five; "D123AB" colored in PURPLE refers to the violation of only one cutoff in lipinski's rule of five; "D123AB" colored in BLACK represents the violation of more than one cutoffs in lipinski's rule of five

Co-Targets

Top

Co-Targets

Co-Targets Info

Target Poor or Non Binders

Top

Target Poor or Non Binders

Target Poor or Non Binders Info

Target Profiles in Patients

Top

Target Expression
Profile (TEP)

Target Expression Profile Info

Target Affiliated Biological Pathways

Top

KEGG Pathway

[+] 1 KEGG Pathways

Neuroactive ligand-receptor interaction

Reactome

[+] 2 Reactome Pathways

Histamine receptors

G alpha (i) signalling events

WikiPathways

[+] 4 WikiPathways

Monoamine Transport

GPCRs, Class A Rhodopsin-like

GPCR ligand binding

GPCR downstream signaling

Target-Related Models and Studies

Top

Target Validation

Target Validation Info

Target QSAR Model

References

Top

REF 1

Effects of pitolisant, a histamine H3 inverse agonist, in drug-resistant idiopathic and symptomatic hypersomnia: a chart review. Sleep Med. 2014 Jun;15(6):681-7.

REF 2

Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2019

REF 3

Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)

REF 4

Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)

REF 5

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: 6927).

REF 6

ClinicalTrials.gov (NCT01018875) Efficacy and Safety Study of ABT-288 in Subjects With Mild-to-Moderate Alzheimer's Disease. U.S. National Institutes of Health.

REF 7

ClinicalTrials.gov (NCT01207115) A Study of ABT-652 in Adults With Osteoarthritis Pain of the Knee. U.S. National Institutes of Health.

REF 8

ClinicalTrials.gov (NCT01548287) A Study of the Safety and Tolerability of AZD5213 Effect on Sleep for Patients With Alzheimer's/Cognitive Impairment. U.S. National Institutes of Health.

REF 9

ClinicalTrials.gov (NCT00566449) A Safety and Effectiveness Study of JNJ-31001074 in Adults With Attention-Deficit/Hyperactivity Disorder.. U.S. National Institutes of Health.

REF 10

ClinicalTrials.gov (NCT01772199) Study to Assess Whether GSK239512 Can Remyelinate Lesions in Subjects With Relapsing Remitting Multiple Sclerosis. U.S. National Institutes of Health.

REF 11

ClinicalTrials.gov (NCT00424931) A Safety and Effectiveness Study of a Single Dose of JNJ-17216498 in Patients With Narcolepsy. U.S. National Institutes of Health.

REF 12

ClinicalTrials.gov (NCT00804687) An Efficacy Study of JNJ-39220675 and Pseudoephedrine in Participants With Allergic Rhinitis. U.S. National Institutes of Health.

REF 13

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800032202)

REF 14

ClinicalTrials.gov (NCT01266525) Effect of Different Doses of SAR110894D on Cognition in Patients With Mild to Moderate Alzheimer's Disease on Donepezil. U.S. National Institutes of Health.

REF 15

REF 16

The histamine H3 receptor: from gene cloning to H3 receptor drugs. Nat Rev Drug Discov. 2005 Feb;4(2):107-20.

REF 17

ClinicalTrials.gov (NCT01093508) Single-dose Safety Study of APD916 in Healthy Volunteers. U.S. National Institutes of Health.

REF 18

Clinical pipeline report, company report or official report of TransTech Pharma (2011).

REF 19

ClinicalTrials.gov (NCT01903824) Pharmacokinetics and Pharmacodynamics (PK/PD) of CEP-26401 in Healthy Subjects. U.S. National Institutes of Health.

REF 20

ClinicalTrials.gov (NCT00887601) BOLD Functional Magnetic Resonance Imaging (fMRI) and Cerebral Blood Flow Measurements as Biomarkers for Cognition Enhancing Drugs (3134-006). U.S. National Institutes of Health.

REF 21

ClinicalTrials.gov (NCT01092780) Pharmacodynamics and Efficacy of MK7288 (MK-7288-010). U.S. National Institutes of Health.

REF 22

(11)C-MK-8278 PET as a tool for pharmacodynamic brain occupancy of histamine 3 receptor inverse agonists. J Nucl Med. 2014 Jan;55(1):65-72.

REF 23

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