Synthesis, in vitro evaluation, and intraocular pressure effects of water-soluble prodrugs of endocannabinoid noladin ether.
The poor aqueous solubility of 2-arachidonyl glyceryl ether (noladin ether) 2 hinders both pharmacological studies and pharmaceutical development. The synthesized mono- and diphosphate esters of noladin ether (4 and 6) considerably increased the aqueous solubility of noladin ether (>40000-fold), showed high stability against chemical hydrolysis in buffer solutions, and were rapidly converted to the parent drug via enzymatic hydrolysis. The monophosphate ester of noladin ether reduced intraocular pressure in normotensive rabbits.
Juntunen
Juha
J
Department of Pharmaceutical Chemistry, University of Kuopio, P.O. Box 1627, FIN-70211 Kuopio, Finland. Juha.Juntunen@uku.fi
Vepsäläinen
Jouko
J
Niemi
Riku
R
Laine
Krista
K
Järvinen
Tomi
T
D000818:Animals; D063385:Cannabinoid Receptor Modulators / Q000378:metabolism*; D063388:Endocannabinoids; D005989:Glycerides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006868:Hydrolysis; D007429:Intraocular Pressure / Q000187:drug effects*; D009883:Ophthalmic Solutions; D011355:Prodrugs / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011817:Rabbits; D012995:Solubility; D013329:Structure-Activity Relationship
D063385:Cannabinoid Receptor Modulators; D063388:Endocannabinoids; D005989:Glycerides; D009883:Ophthalmic Solutions; D011355:Prodrugs; C424442:noladin ether