Altropane

Identification

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Name
Altropane
Accession Number
DB04947
Type
Small Molecule
Groups
Investigational
Description

Boston Life Sciences (BLS) is developing Altropane as a potential radio-imaging agent to be used with single photon emission tomography (SPECT), for the early diagnosis of Parkinson's disease (PD) and attention deficit hyperactivity disorder (ADHD).

Structure
Thumb
Synonyms
Not Available
Categories
UNII
1Q4092099O
CAS number
180468-34-2
Weight
Average: 429.2677
Monoisotopic: 429.060100546
Chemical Formula
C18H21FINO2
InChI Key
GTQLIPQFXVKRKJ-UNSMHXHVSA-N
InChI
InChI=1S/C18H21FINO2/c1-23-18(22)17-15(12-3-5-13(19)6-4-12)11-14-7-8-16(17)21(14)10-2-9-20/h2-6,9,14-17H,7-8,10-11H2,1H3/b9-2+/t14-,15+,16+,17-/m0/s1
IUPAC Name
methyl (1R,2S,3S,5S)-3-(4-fluorophenyl)-8-[(2E)-3-iodoprop-2-en-1-yl]-8-azabicyclo[3.2.1]octane-2-carboxylate
SMILES
[H][C@]12CC[C@]([H])([C@H]([C@H](C1)C1=CC=C(F)C=C1)C(=O)OC)N2C\C=C\I

Pharmacology

Indication

Investigated for use/treatment in attention deficit/hyperactivity disorder (ADHD), parkinson's disease, and pediatric indications.

Pharmacodynamics

Altropane is a molecular-imaging agent that specifically binds to the dopamine transporter (DAT) protein found on the surface of dopamine-producing neurons, making it visible during SPECT imaging. Since most forms of Parkinsonian Syndromes result in a decreased number of dopamine-producing cells, it would be expected that these patients also have fewer DATs than do patients without PS. Thus, it is believed that altropane used in conjunction with SPECT imaging could be a useful test to distinguish Parkinsonian Syndrome tremors from non-Parkinsonian tremor: non-Parkinsonian patients would have more altropane-binding visible in the SPECT image, while Parkinsonian patients would have less.

Mechanism of action

Positron emission tomography (PET) cameras are expensive and scarce, and the tests are non-reimbursable. A less costly and more available test such as a single photon emission computed tomography (SPECT) may be helpful in the diagnosis of early or atypical Parkinson's disease (PD) if its sensitivity is comparable to a PET scan. Altropane is an iodinated form of the N-allyl analog of WIN 35,428 which acts as a dopamine transport inhibitor. When radiolabeled with the gamma emitting isotope [123I], altropane serves as a SPECT ligand with high affinity and selectivity for the dopamine transporter. It is a good marker for dopamine neurons and is useful in detecting PD.

TargetActionsOrganism
USodium-dependent dopamine transporterNot AvailableHumans
Absorption
Not Available
Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Not Available
Route of elimination
Not Available
Half life
Not Available
Clearance
Not Available
Toxicity
Not Available
Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
Not Available
Food Interactions
Not Available

References

General References
  1. Cattabeni F: Altropane (Boston Life Science). Curr Opin Investig Drugs. 2002 Nov;3(11):1647-51. [PubMed:12476968]
  2. Fernandez HH, Friedman JH, Fischman AJ, Noto RB, Lannon MC: Is altropane SPECT more sensitive to fluoroDOPA PET for detecting early Parkinson's disease? Med Sci Monit. 2001 Nov-Dec;7(6):1339-43. [PubMed:11687754]
  3. Madras BK, Gracz LM, Fahey MA, Elmaleh D, Meltzer PC, Liang AY, Stopa EG, Babich J, Fischman AJ: Altropane, a SPECT or PET imaging probe for dopamine neurons: III. Human dopamine transporter in postmortem normal and Parkinson's diseased brain. Synapse. 1998 Jun;29(2):116-27. [PubMed:9593102]
  4. Fischman AJ, Bonab AA, Babich JW, Livni E, Alpert NM, Meltzer PC, Madras BK: [(11)C, (127)I] Altropane: a highly selective ligand for PET imaging of dopamine transporter sites. Synapse. 2001 Mar 15;39(4):332-42. [PubMed:11169784]
  5. Madras BK, Meltzer PC, Liang AY, Elmaleh DR, Babich J, Fischman AJ: Altropane, a SPECT or PET imaging probe for dopamine neurons: I. Dopamine transporter binding in primate brain. Synapse. 1998 Jun;29(2):93-104. [PubMed:9593100]
  6. Madras BK, Gracz LM, Meltzer PC, Liang AY, Elmaleh DR, Kaufman MJ, Fischman AJ: Altropane, a SPECT or PET imaging probe for dopamine neurons: II. Distribution to dopamine-rich regions of primate brain. Synapse. 1998 Jun;29(2):105-15. [PubMed:9593101]
  7. Fischman AJ, Bonab AA, Babich JW, Palmer EP, Alpert NM, Elmaleh DR, Callahan RJ, Barrow SA, Graham W, Meltzer PC, Hanson RN, Madras BK: Rapid detection of Parkinson's disease by SPECT with altropane: a selective ligand for dopamine transporters. Synapse. 1998 Jun;29(2):128-41. [PubMed:9593103]
External Links
PubChem Compound
6440180
PubChem Substance
175426914
ChemSpider
4944487
ChEBI
135696
Wikipedia
Altropane

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
2CompletedDiagnosticParkinson's Disease (PD)1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.0081 mg/mLALOGPS
logP4.05ALOGPS
logP3.95ChemAxon
logS-4.7ALOGPS
pKa (Strongest Basic)7.59ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area29.54 Å2ChemAxon
Rotatable Bond Count5ChemAxon
Refractivity97.34 m3·mol-1ChemAxon
Polarizability37.12 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9925
Blood Brain Barrier+0.9807
Caco-2 permeable+0.5405
P-glycoprotein substrateNon-substrate0.5265
P-glycoprotein inhibitor IInhibitor0.8581
P-glycoprotein inhibitor IIInhibitor0.756
Renal organic cation transporterInhibitor0.6782
CYP450 2C9 substrateNon-substrate0.7524
CYP450 2D6 substrateNon-substrate0.6614
CYP450 3A4 substrateSubstrate0.6347
CYP450 1A2 substrateInhibitor0.5323
CYP450 2C9 inhibitorNon-inhibitor0.6098
CYP450 2D6 inhibitorNon-inhibitor0.6468
CYP450 2C19 inhibitorInhibitor0.5619
CYP450 3A4 inhibitorNon-inhibitor0.8397
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.6144
Ames testNon AMES toxic0.7037
CarcinogenicityNon-carcinogens0.9281
BiodegradationNot ready biodegradable1.0
Rat acute toxicity2.8285 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.7373
hERG inhibition (predictor II)Inhibitor0.5528
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as phenyltropanes. These are compounds containing a phenyl group linked to a tropane moiety. Tropane is an organonitrogenous [3.2.1] bicyclic organic compound.
Kingdom
Organic compounds
Super Class
Alkaloids and derivatives
Class
Tropane alkaloids
Sub Class
Phenyltropanes
Direct Parent
Phenyltropanes
Alternative Parents
Phenylpiperidines / Piperidinecarboxylic acids / Aralkylamines / Fluorobenzenes / Aryl fluorides / N-alkylpyrrolidines / Methyl esters / Trialkylamines / Amino acids and derivatives / Vinyl iodides
show 9 more
Substituents
Phenyltropane / Phenylpiperidine / Piperidinecarboxylic acid / Fluorobenzene / Halobenzene / Aralkylamine / Aryl fluoride / Aryl halide / Monocyclic benzene moiety / Benzenoid
show 29 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
Not Available

Targets

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
General Function
Monoamine transmembrane transporter activity
Specific Function
Amine transporter. Terminates the action of dopamine by its high affinity sodium-dependent reuptake into presynaptic terminals.
Gene Name
SLC6A3
Uniprot ID
Q01959
Uniprot Name
Sodium-dependent dopamine transporter
Molecular Weight
68494.255 Da
References
  1. Spencer TJ, Biederman J, Madras BK, Dougherty DD, Bonab AA, Livni E, Meltzer PC, Martin J, Rauch S, Fischman AJ: Further evidence of dopamine transporter dysregulation in ADHD: a controlled PET imaging study using altropane. Biol Psychiatry. 2007 Nov 1;62(9):1059-61. Epub 2007 May 23. [PubMed:17511972]

Drug created on October 21, 2007 16:23 / Updated on June 04, 2019 06:13