Table 1.

Effects of 76 compounds with different biological actions upon the activity of human recombinant MGL (lysate assay, 0.25 mM NPA as substrate)

		MGL activity (% of control)
Compound	Primary pharmacological action	3 µM	10 µM
CB/TRPV1 receptor ligands and related compounds
ACEA	CB1 receptor agonist	126	81
AM251	CB1 receptor inverse agonist	69	62
AM404**	Blocks endocannabinoid reuptake	63	18
AM630	CB2 receptor inverse agonist	90	55
N-arachidonoyl serotonin	FAAH and TRPV1 inhibitor	37	32
N-arachidonoyl dopamine**	Endogenous TRPV1 ligand	15	−6
Capsazepine	TRPV1 antagonist	90	63
CP 55,940**	Non-selective CB receptor agonist	28	26
JWH015**	CB2 receptor agonist	53	37
JWH133a	CB2 receptor agonist	172	170
(±)-2-Methylarachidonyl-2′-fluoroethylamide	CB1 receptor agonist	89	99
Resveratrol	Antioxidant, CB1 receptor ligand	101	86
RHC-80267	DAG lipase inhibitor	102	71
(±)SLV 319	CB1 receptor inverse agonist	99	79
Tetrahydrolipstatin	Lipase inhibitor (incl. DAG lipase)	95	37
Win 55,212-2 mesylate**	Non-selective CB receptor agonist	67	25
Non-steroidal anti-inflammatory drugs
Acetylsalicylic acid*, diclofenac, dipyrone, fenbufen*, fenoprofen, flufenamic acid, ketoprofen*, meloxicam*, nabumetone, niflumic acid, nimesulide, sulindac, suprofen	Inhibition of cyclooxygenase	range 76–147	range 95–161
Antidepressants
Amitriptyline, clomipramine, desipramine, imipramine, nortriptyline, maprotiline	Monoamine reuptake inhibitors	range 82–120	range 78–122
Phenelzine	Monoamine oxidase inhibitor
Other CNS-active drugs and related compounds
Haloperidol, cis-(Z)-flupenthixol	Dopamine receptor antagonists	range 86–116	range 72–116
Spiperone*	DA/5-HT1A receptor antagonists
Ketanserin, pirenperone*	5-HT2 receptor antagonists
Promethazine	Histamine H1 receptor antagonist
Diazepam, flurazepam, temazepam	Benzodiazepines
Sodium barbital	Barbiturate
Nipecotic acid	GABA reuptake inhibitor
(+)MK801	NMDA receptor antagonist
Naloxone	Opioid receptor antagonist
Physostigmine sulphate	Acetylcholinesterase inhibitor
Other drugs and related compounds
Lidocaine, tetracaine	Na+-channel blockers	range 87–170	range 90–114
Verapamil	L-type Ca2+ channel blocker
Lovastatin	HMG-CoA reductase inhibitor
S(−)Atenolol, R(+)atenolol	ß-Adrenoceptor antagonists (S>R)
Captopril	ACE inhibitor
Theophylline, 8-phenyltheophylline	Adenosine receptor antagonists
Cromolyn sodium	‘Mast cell stabiliser’
Progesterone	Sex steroid hormone
Troglitazone**	PPARγ ligand	21	2
Naturally occurring, biologically active compounds
Coumestrol	Non-steroidal phytoestrogen	range 74–99	range 45–143
Baicalein, fisetin, luteolin, morin, phloretin, quercetin	Flavonoids; antioxidant and other properties
Other compounds (a selection)
3-Hydroxytyramine		Range 92–126	range 76–103
Benzamide
Hydrocinnamic acid
N-Acetyl-D-sphingosine
8-Methyl-N-vanillyl-6-noneamide
Thimerosal		61	45

Data are for single experiments, albeit run on different plates for the 3 µM and the 10 µM test concentrations, with ‘hits’ (>60% inhibition at the test concentration shown) given in bold text. Selected compounds (marked with asterisks) were retested at a later date at a concentration of either 10 µM (inactive compounds, *) or over a concentration range (**, compounds shown in Figure 1A) to confirm the reliability, but the values shown here are from the initial experiments.

^aJWH133 was also retested at a later stage, and the % of control activities seen after 0, 30 and 60 min pre-incubation, respectively, were: 3 µM, 100 ± 17, 129 ± 17 and 133 ± 25; 10 µM, 98 ± 20, 146 ± 8 and 159 ± 21 (means ± SEM, n = 3).