Cannabinoid-based drugs targeting CB1 and TRPV1, the sympathetic nervous system, and arthritis

Table 1 Characteristics of selected cannabinoid receptor ligands

Ligand	Target receptors	Ki at CB₁ in nM	Ki at CB₂ in nM	E_max/IC₅₀ at TRPV1 (nM)	Route of degradation
Anandamide	CB₁, CB₂, GPR55, TRPV1, TRPA1, TRPM8 (antagonist)	239.2 ± 61.77 [158]	439.5 ± 95.89 [158]	458 (E_max) [159]	FAAH, FAAH-2, NAAA, COX-2, LOX [160]
2-AG	CB₁, CB₂, TRPV1, GABAA	3423.6 ± 3288.24 [158]	1193.8 ± 327.71 [158]	750 ± 40 (IC₅₀) [161]	MAGL, COX-2, LOX, ABHD6/12 [160,162]
Delta9-THC	CB₁, CB₂, GPR18	25.1 ± 5.54 [158]	35.2 ± 5.86 [158]	NA	CYP2C [163]
Rimonabant	CB₁, MOR	1.98 ± 0.36 [164]	NA	NA	CYP3A [165]

Anandamide, 2-arachidonylglycerol (2-AG) and tetrahydrocannabinol (THC) are CB₁/CB₂ agonists, rimonabant is a CB₁/MOR antagonist/inverse agonist. Anandamide and THC are partial CB₁/CB₂ agonists, 2-AG is a full agonist at both receptors. The main degrading enzyme for each compound is highlighted in bold. ABHD, α/β-hydrolase domain; CB ₁ /CB ₂, cannabinoid receptor I/II; COX-2, cyclooxygenase-2; CYP, cytochrome P450; Delta9 THC, delta9 tetrahydrocannabinol; Emax, maximal functional response; FAAH, fatty acid amide hydrolase; IC50, half maximal inhibitory concentration; Ki, dissociation constant; LOX, lipoxygenase; MAGL, monoacylglycerol lipase; MOR, μ opoid receptor; NA, not applicable; NAAA, N-acylethanolamine-hydrolyzing acid amidase; TRPA1, transient receptor potential ankyrin I; TRPM8, transient receptor potential melastatin 8; TRPV1, transient receptor potential vanilloid I

ISSN: 1478-6362