Identification

Name
Tenocyclidine
Accession Number
DB01520
Type
Small Molecule
Groups
Experimental, Illicit
Description

Tenocyclidine (TCP, thienyl cyclohexylpiperidine) is a dissociative anesthetic drug with stimulant and hallucinogenic effects. It is similar in effects to phencyclidine but is considerably more potent. Due to its similarity in effects to PCP, TCP was placed into the Schedule I list of illegal drugs in the 1970s, although it was only briefly abused in the 1970s and 1980s and is now little known. [Wikipedia]

Structure
Thumb
Synonyms
  • TCP
Product Ingredients
IngredientUNIICASInChI Key
Tenocyclidine hydrochloride425WW340S2 1867-65-8IIPLEZRBGQCZMF-UHFFFAOYSA-N
Categories
UNII
8BQ45Q6VCL
CAS number
21500-98-1
Weight
Average: 249.415
Monoisotopic: 249.155120431
Chemical Formula
C15H23NS
InChI Key
JUZZEWSCNBCFRL-UHFFFAOYSA-N
InChI
InChI=1S/C15H23NS/c1-3-9-15(10-4-1,14-8-7-13-17-14)16-11-5-2-6-12-16/h7-8,13H,1-6,9-12H2
IUPAC Name
1-[1-(thiophen-2-yl)cyclohexyl]piperidine
SMILES
C1CCN(CC1)C1(CCCCC1)C1=CC=CS1

Pharmacology

Indication

Because of its high affinity for the phencyclidine binding site on the NMDA receptor, the 3H radiolabelled form of tenocyclidine is widely used in research into NMDA receptors.

Structured Indications
Not Available
Pharmacodynamics

Tenocyclidine (TCP) has slightly different binding properties to phencyclidine (PCP), with more affinity for NMDA receptors but less affinity for sigma receptors.

Mechanism of action

The primary interactions are as a non-competitive antagonist at the 3A-subunit of the NMDAR in Homo sapiens. TCP is known to bind, with relatively high affinity, to the D1 subunit of the human DAT, in addition to displaying a positive antagonistic effect at the α7-subunit of the Nicotinic Acetylcholine Receptor (nAChR). It also binds to the mu-opioid receptor, which seems to be a central part of the mechanism of action of drugs in this class. (For example, Dizocilpine [MK-801] shows little appreciable analgesic effect despite having a high specificity for the NMDA-3A and NMDA-3B subunits - this may well be mediated by the lack of related efficacy at the mu-opioid receptor, though the NMDAR certainly does play a role in transmission of pain signals).

TargetActionsOrganism
AGlutamate receptor ionotropic, NMDA 3A
antagonist
Human
AGlutamate receptor ionotropic, NMDA 3B
antagonist
Human
AGlutamate receptor ionotropic, NMDA 2A
antagonist
Human
AGlutamate receptor ionotropic, NMDA 2C
antagonist
Human
AGlutamate receptor ionotropic, NMDA 2B
antagonist
Human
UGlutamate receptor ionotropic, NMDA 2D
antagonist
Human
UAlpha-7 nicotinic cholinergic receptor subunit
antagonist
Human
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

Synthesis Reference
Not Available
General References
Not Available
External Links
PubChem Compound
62751
PubChem Substance
46505124
ChemSpider
56495
BindingDB
50004107
ChEBI
64610
ChEMBL
CHEMBL279676
Wikipedia
Tenocyclidine
ATC Codes
Not Available
AHFS Codes
Not Available
PDB Entries
Not Available
FDA label
Not Available
MSDS
Not Available

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1RecruitingTreatmentAcute Myelogenous Leukaemia (AML) / Leukemias / Myelodysplastic Syndromes1
1, 2RecruitingTreatmentLeukemia Acute Myeloid Leukemia (AML) / Myelodysplastic Syndrome1

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 Solubility0.0313 mg/mLALOGPS
logP5.04ALOGPS
logP4.4ChemAxon
logS-3.9ALOGPS
pKa (Strongest Basic)10.44ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count1ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area3.24 Å2ChemAxon
Rotatable Bond Count2ChemAxon
Refractivity74.54 m3·mol-1ChemAxon
Polarizability29.28 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9928
Blood Brain Barrier+0.9938
Caco-2 permeable+0.7111
P-glycoprotein substrateSubstrate0.5415
P-glycoprotein inhibitor INon-inhibitor0.6979
P-glycoprotein inhibitor IINon-inhibitor0.6053
Renal organic cation transporterInhibitor0.7012
CYP450 2C9 substrateNon-substrate0.779
CYP450 2D6 substrateNon-substrate0.7953
CYP450 3A4 substrateNon-substrate0.5754
CYP450 1A2 substrateNon-inhibitor0.7973
CYP450 2C9 inhibitorNon-inhibitor0.8693
CYP450 2D6 inhibitorInhibitor0.8978
CYP450 2C19 inhibitorNon-inhibitor0.7375
CYP450 3A4 inhibitorNon-inhibitor0.8308
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.9405
Ames testNon AMES toxic0.7056
CarcinogenicityNon-carcinogens0.9387
BiodegradationNot ready biodegradable0.9905
Rat acute toxicity3.1153 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.906
hERG inhibition (predictor II)Inhibitor0.5873
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 chemical entities known as aralkylamines. These are alkylamines in which the alkyl group is substituted at one carbon atom by an aromatic hydrocarbyl group.
Kingdom
Chemical entities
Super Class
Organic compounds
Class
Organic nitrogen compounds
Sub Class
Organonitrogen compounds
Direct Parent
Aralkylamines
Alternative Parents
Cyclohexylamines / Piperidines / Thiophenes / Heteroaromatic compounds / Trialkylamines / Azacyclic compounds / Organopnictogen compounds / Hydrocarbon derivatives
Substituents
Aralkylamine / Cyclohexylamine / Piperidine / Heteroaromatic compound / Thiophene / Tertiary aliphatic amine / Tertiary amine / Azacycle / Organoheterocyclic compound / Organopnictogen compound
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
piperidines, tertiary amino compound, thiophenes (CHEBI:64610 )

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Antagonist
General Function
Protein phosphatase 2a binding
Specific Function
NMDA receptor subtype of glutamate-gated ion channels with reduced single-channel conductance, low calcium permeability and low voltage-dependent sensitivity to magnesium. Mediated by glycine. May ...
Gene Name
GRIN3A
Uniprot ID
Q8TCU5
Uniprot Name
Glutamate receptor ionotropic, NMDA 3A
Molecular Weight
125464.07 Da
References
  1. Stirling JM, Cross AJ, Green AR: The binding of [3H]thienyl cyclohexylpiperidine ([3H]TCP) to the NMDA-phencyclidine receptor complex. Neuropharmacology. 1989 Jan;28(1):1-7. [PubMed:2538766 ]
  2. Geldenhuys WJ, Malan SF, Bloomquist JR, Van der Schyf CJ: Structure-activity relationships of pentacycloundecylamines at the N-methyl-d-aspartate receptor. Bioorg Med Chem. 2007 Feb 1;15(3):1525-32. Epub 2006 Sep 29. [PubMed:17157509 ]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Antagonist
General Function
Nmda glutamate receptor activity
Specific Function
NMDA receptor subtype of glutamate-gated ion channels with reduced single-channel conductance, low calcium permeability and low voltage-dependent sensitivity to magnesium. Mediated by glycine.
Gene Name
GRIN3B
Uniprot ID
O60391
Uniprot Name
Glutamate receptor ionotropic, NMDA 3B
Molecular Weight
112990.98 Da
References
  1. Stirling JM, Cross AJ, Green AR: The binding of [3H]thienyl cyclohexylpiperidine ([3H]TCP) to the NMDA-phencyclidine receptor complex. Neuropharmacology. 1989 Jan;28(1):1-7. [PubMed:2538766 ]
  2. Geldenhuys WJ, Malan SF, Bloomquist JR, Van der Schyf CJ: Structure-activity relationships of pentacycloundecylamines at the N-methyl-d-aspartate receptor. Bioorg Med Chem. 2007 Feb 1;15(3):1525-32. Epub 2006 Sep 29. [PubMed:17157509 ]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Antagonist
General Function
Zinc ion binding
Specific Function
NMDA receptor subtype of glutamate-gated ion channels possesses high calcium permeability and voltage-dependent sensitivity to magnesium. Activation requires binding of agonist to both types of sub...
Gene Name
GRIN2A
Uniprot ID
Q12879
Uniprot Name
Glutamate receptor ionotropic, NMDA 2A
Molecular Weight
165281.215 Da
References
  1. Stirling JM, Cross AJ, Green AR: The binding of [3H]thienyl cyclohexylpiperidine ([3H]TCP) to the NMDA-phencyclidine receptor complex. Neuropharmacology. 1989 Jan;28(1):1-7. [PubMed:2538766 ]
  2. Geldenhuys WJ, Malan SF, Bloomquist JR, Van der Schyf CJ: Structure-activity relationships of pentacycloundecylamines at the N-methyl-d-aspartate receptor. Bioorg Med Chem. 2007 Feb 1;15(3):1525-32. Epub 2006 Sep 29. [PubMed:17157509 ]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Antagonist
General Function
Nmda glutamate receptor activity
Specific Function
NMDA receptor subtype of glutamate-gated ion channels with high calcium permeability and voltage-dependent sensitivity to magnesium. Mediated by glycine.
Gene Name
GRIN2C
Uniprot ID
Q14957
Uniprot Name
Glutamate receptor ionotropic, NMDA 2C
Molecular Weight
134207.77 Da
References
  1. Stirling JM, Cross AJ, Green AR: The binding of [3H]thienyl cyclohexylpiperidine ([3H]TCP) to the NMDA-phencyclidine receptor complex. Neuropharmacology. 1989 Jan;28(1):1-7. [PubMed:2538766 ]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Antagonist
General Function
Zinc ion binding
Specific Function
NMDA receptor subtype of glutamate-gated ion channels with high calcium permeability and voltage-dependent sensitivity to magnesium. Mediated by glycine. In concert with DAPK1 at extrasynaptic site...
Gene Name
GRIN2B
Uniprot ID
Q13224
Uniprot Name
Glutamate receptor ionotropic, NMDA 2B
Molecular Weight
166365.885 Da
References
  1. Stirling JM, Cross AJ, Green AR: The binding of [3H]thienyl cyclohexylpiperidine ([3H]TCP) to the NMDA-phencyclidine receptor complex. Neuropharmacology. 1989 Jan;28(1):1-7. [PubMed:2538766 ]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Antagonist
General Function
Nmda glutamate receptor activity
Specific Function
NMDA receptor subtype of glutamate-gated ion channels with high calcium permeability and voltage-dependent sensitivity to magnesium. Mediated by glycine.
Gene Name
GRIN2D
Uniprot ID
O15399
Uniprot Name
Glutamate receptor ionotropic, NMDA 2D
Molecular Weight
143750.685 Da
References
  1. Stirling JM, Cross AJ, Green AR: The binding of [3H]thienyl cyclohexylpiperidine ([3H]TCP) to the NMDA-phencyclidine receptor complex. Neuropharmacology. 1989 Jan;28(1):1-7. [PubMed:2538766 ]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Antagonist
General Function
Not Available
Specific Function
Not Available
Gene Name
CHRNA7
Uniprot ID
Q693P7
Uniprot Name
Alpha-7 nicotinic cholinergic receptor subunit
Molecular Weight
2987.635 Da
References
  1. Pagan OR, Eterovic VA, Garcia M, Vergne D, Basilio CM, Rodriguez AD, Hann RM: Cembranoid and long-chain alkanol sites on the nicotinic acetylcholine receptor and their allosteric interaction. Biochemistry. 2001 Sep 18;40(37):11121-30. [PubMed:11551210 ]

Drug created on July 31, 2007 07:10 / Updated on October 02, 2017 04:59