AM-1235 (1-(5-fluoropentyl)-3-(naphthalen-1-oyl)-6-nitroindole) is a drug that acts as a potent and reasonably selective

agonist An agonist is a chemical that activates a receptor to produce a biological response. Receptors are cellular proteins whose activation causes the cell to modify what it is currently doing. In contrast, an antagonist blocks the action of the ago ...

for the

cannabinoid receptor Cannabinoid receptors, located throughout the body, are part of the endocannabinoid system a class of cell membrane receptors in the G protein-coupled receptor superfamily. As is typical of G protein-coupled receptors, the cannabinoid recepto ...

CB₁.

Pharmacology

Pharmacodynamics

AM-1235 is a

with K_i of 1.5 nM at CB₁ compared to 20.4 nM at CB₂. While the 6-nitro substitution on the

indole Indole is an aromatic heterocyclic organic compound with the formula C8 H7 N. It has a bicyclic structure, consisting of a six-membered benzene ring fused to a five-membered pyrrole ring. Indole is widely distributed in the natural environmen ...

ring reduces affinity for both CB₁ and CB₂ relative to the unsubstituted parent compound

AM-2201 AM-2201 (1-(5-fluoropentyl)-3-(1-naphthoyl)indole) is a recreational designer drug that acts as a potent but nonselective full agonist for the cannabinoid receptor. It is part of the AM series of cannabinoids discovered by Alexandros Makriyanni ...

, CB₂ affinity is reduced much more, resulting in a CB₁ selectivity of around 13 times. This is in contrast to other related compounds such as

AM-1221 AM-1221 is a drug that acts as a potent and selective agonist for the cannabinoid receptor CB2, with a ''K''i of 0.28 nM at CB2 and 52.3 nM at the CB1 receptor, giving it around 180 times selectivity for CB2. The 2- methyl and 6-nit ...

where a 6-nitro substitution instead confers significant selectivity for CB₂.

Pharmacokinetics

AM-1235

metabolism Metabolism (, from el, μεταβολή ''metabolē'', "change") is the set of life-sustaining chemical reactions in organisms. The three main functions of metabolism are: the conversion of the energy in food to energy available to run cell ...

differs only slightly from that of

JWH-018 JWH-018 (1-pentyl-3-(1-naphthoyl)indole, NA-PIMO or AM-678) is an analgesic chemical from the naphthoylindole family that acts as a full agonist at both the CB1 and CB2 cannabinoid receptors, with some selectivity for CB2. It produces effects in a ...

. AM-1235 ''N''-

dealkylation Alkylation is the transfer of an alkyl group from one molecule to another. The alkyl group may be transferred as an alkyl carbocation, a free radical, a carbanion, or a carbene (or their equivalents). Alkylating agents are reagents for effecting al ...

produces fluoropentane instead of

pentane Pentane is an organic compound with the formula C5H12—that is, an alkane with five carbon atoms. The term may refer to any of three structural isomers, or to a mixture of them: in the IUPAC nomenclature, however, pentane means exclusively the ' ...

(or plain

alkane In organic chemistry, an alkane, or paraffin (a historical trivial name that also has other meanings), is an acyclic saturated hydrocarbon. In other words, an alkane consists of hydrogen and carbon atoms arranged in a tree structure in which ...

s in general). It has been speculated that the fluoropentane might function as an

alkylating agent Alkylation is the transfer of an alkyl group from one molecule to another. The alkyl group may be transferred as an alkyl carbocation, a free radical, a carbanion, or a carbene (or their equivalents). Alkylating agents are reagents for effecting al ...

or is further metabolized into toxic

fluoroacetic acid Fluoroacetic acid is a organofluorine compound with formula CH2FCO2H. It is a colorless solid that is noted for its relatively high toxicity. The conjugate base, fluoroacetate occurs naturally in at least 40 plants in Australia, Brazil, and Afric ...

. This is not true since

fluoroalkane Organofluorine chemistry describes the chemistry of the organofluorines, organic compounds that contain the carbon–fluorine bond. Organofluorine compounds find diverse applications ranging from oil and water repellents to pharmaceuticals, ref ...

s do not act as

s under normal conditions and uneven

chains metabolize into substantially less toxic fluoropropanoic acid.

Legal status

In the United States, all CB₁ receptor agonists of the 3-(1-naphthoyl)indole class such as AM-1235 are

Schedule I Controlled Substance This is the list of Schedule I drugs as defined by the United States Controlled Substances Act. 21 CFRbr>1308.11(CSA Sched I) with changes through (Oct 18, 2012). Retrieved September 6, 2013. The following findings are required for drugs to be pl ...

Pharmacology

Pharmacodynamics

Pharmacokinetics

Legal status

See also