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Research tools

AM281

Selective antagonist and inverse agonist of the CB1 receptor, used as a SPECT imaging radioligand.

Unscheduled
Level of detail

Harm-reduction warning

No characterised human dose: animal / in vitro data only. Effect profile, safety margin and acute toxicity are not documented in human clinical practice. Extremely potent compound: severe effects, seizures and deaths reported in the literature.

C₂₁H₁₉Cl₂IN₄O₂

CAS 202463-68-1

Family
ECS pharmacological toolAntagonist or inverse agonist
Molar mass
557.20 g/mol

Updated on

In plain terms

AM281 is a laboratory molecule, made entirely by synthesis: it does not exist in hemp. It blocks the CB1 receptor, the one THC activates, and was designed as a radioactive tracer making these receptors visible in the brain during imaging examinations. It is not a consumer product.

Receptors and activity

Target network

CB1AntagonistKi = 12 nMbrain membranes; species not specified in the abstract; blocks the response of guinea pig small intestine to a cannabinoid agonist
  • Blocks or inhibits
  • Binds or modulates

The lower the cited value, the closer the target sits to AM281: one ring per factor of 100. A target with no measured value stays on the edge.

Where these targets live

Where each target has been found in humans, according to the cited studies. The map shows the target, not an effect of AM281.

Brain, side view
Body, front view
Blood

CB1CB1 found in 7 regions of the body

  1. Basal gangliadenseMost dense in basal ganglia outflow nuclei1
  2. CerebellumdenseVery dense in the cerebellum1
  3. HippocampusdenseVery high concentrations in the hippocampus2
  4. AmygdaladenseHigh concentrations in the amygdala2
  5. CortexpresentPresent throughout the neocortex2
  6. Adipose tissuepresentExpressed in adipose tissue3
  7. GutpresentColonic epithelium, smooth muscle and plexus4

Map sources

  1. Herkenham M et al. Cannabinoid receptor localization in brain. Proc Natl Acad Sci U S A, 1990 (new tab)
  2. Glass M et al. Cannabinoid receptors in the human brain: a detailed anatomical and quantitative autoradiographic study in the fetal, neonatal and adult human brain. Neuroscience, 1997 (new tab)
  3. Engeli S et al. Activation of the peripheral endocannabinoid system in human obesity. Diabetes, 2005 (new tab)
  4. Wright K et al. Differential expression of cannabinoid receptors in the human colon: cannabinoids promote epithelial wound healing. Gastroenterology, 2005 (new tab)

Cited values

  1. CB1AntagonistKi = 12 nM65 out of 100

    Lan et al., AAPS PharmSci 1999 (new tab) · brain membranes; species not specified in the abstract; blocks the response of guinea pig small intestine to a cannabinoid agonist

  2. CB2Binding (function not established)Ki = 4.2 µM23 out of 100

    Lan et al., AAPS PharmSci 1999 (new tab) · spleen membranes; species not specified in the abstract

  3. GPR55Modulatorno measured value cited
Bar length follows the measured value (Ki, Kd, EC50 or IC50), on one scale shared by every entry, from 100 µM to 0.1 nM. A target with no cited value has no bar.

Pharmacology

AM281 is a diaryl pyrazole-3-carboxamide, an analogue of rimonabant (SR141716A), synthesised in 1999 as a candidate radioligand for SPECT imaging of CB1 receptors (Lan et al. 1999). On membrane preparations its Ki is 12 nM at CB1 (brain) and 4,200 nM at CB2 (spleen), a selectivity of about 350-fold; it blocks the response of guinea-pig small intestine to a cannabinoid agonist. In animals, intravenous AM281 (0.3 mg/kg) abolished the reduction in locomotor activity induced by WIN 55,212-2 and, alone, roughly doubled locomotor activity between 60 and 120 minutes, an observation the authors interpreted as a sign of an endogenous cannabinoid tone (Cosenza et al. 2000). Labelled with iodine-123, it gave brain SPECT images in baboons (Lan et al. 1999), then detectable specific binding in six patients with Tourette syndrome, with an estimated effective dose of 0.011 mSv/MBq (Berding et al. 2004). Its effect at GPR55 is discordant across assays (Anavi-Goffer et al. 2012).

Key sources.

History

Source
A synthetic molecule of the diaryl pyrazole-3-carboxamide class, an analogue of SR141716A (rimonabant); absent from hemp and from any living organism. A research reagent and precursor of radioligands ([123I]AM281, [131I]AM281).

Origin

Research tool

No known biological pathway: a synthetic molecule of the diaryl pyrazole-3-carboxamide class, an analogue of rimonabant.

Classification

Family, origin and source verification

Family

ECS pharmacological tool › Antagonist or inverse agonist

Verification

Classification, sources and binding values checked on 20 October 2026; text read against its sources and Wikipedia.

Wikipedia (English)

No dedicated article.

References

  1. Lan R, Gatley J, Lu Q, Fan P, Fernando SR, Volkow ND, Pertwee R, Makriyannis A. Design and synthesis of the CB1 selective cannabinoid antagonist AM281: a potential human SPECT ligand. AAPS PharmSci, 1999 (new tab)PMID 11741201
  2. Cosenza M, Gifford AN, Gatley SJ, Pyatt B, Liu Q, Makriyannis A, Volkow ND. Locomotor activity and occupancy of brain cannabinoid CB1 receptors by the antagonist/inverse agonist AM281. Synapse, 2000 (new tab)PMID 11044895
  3. Berding G et al. [123I]AM281 SPECT imaging of central cannabinoid CB1 receptors before and after Delta9-THC therapy and whole-body scanning for assessment of radiation dose in Tourette patients. Biological Psychiatry, 2004 (new tab)PMID 15110734
  4. Anavi-Goffer S et al. Modulation of L-alpha-lysophosphatidylinositol/GPR55 MAPK signaling by cannabinoids. Journal of Biological Chemistry, 2012 (new tab)PMID 22027819
  5. ANSM, Consolidated list of substances classified as narcotics, updated 16 February 2026, annex IV (new tab)
  6. PubChem, compound CID 4302962 (AM 281) (new tab)

Identifiers

Names

IUPAC name
1-(2,4-dichlorophenyl)-5-(4-iodophenyl)-4-methyl-N-morpholin-4-ylpyrazole-3-carboxamide
Other names
AM 281 · AM-281 · [123I]AM281

Identifiers

Formula
C₂₁H₁₉Cl₂IN₄O₂
CAS
202463-68-1
PubChem CID
4302962(new tab)
InChIKey
AJFFBPZYXRNAIC-UHFFFAOYSA-N
SMILES
CC1=C(N(N=C1C(=O)NN2CCOCC2)C3=C(C=C(C=C3)Cl)Cl)C4=CC=C(C=C4)I

Machine-readable entry (JSON)

LLM ingestion format: a structured superset of the entry (identifiers, binding, versioned legal status). Full corpus.