Oxaprotiline (developmental code name C 49-802 BDA), also known as hydroxymaprotiline, is a norepinephrine reuptake inhibitor of the tetracyclic antidepressant (TeCA) family that is related to maprotiline. Though investigated as an antidepressant,[1] it was never marketed.
Dextroprotiline acts as a potentnorepinephrine reuptake inhibitor[2][3] and H1 receptorantagonist,[4] as well as a very weak α1-adrenergic receptorantagonist.[2][5] It has negligible affinity for the serotonin transporter,[2]dopamine transporter, α2-adrenergic receptor,[2][5] and muscarinic acetylcholine receptors.[5] Whether it has any antagonistic effects on the 5-HT2, 5-HT7, or D2 receptors like its relative maprotiline is unclear.
Levoprotiline acts as a selectiveH1 receptorantagonist, with no affinity for adrenaline, dopamine, muscarinic acetylcholine, or serotoninreceptors, or any of the monoamine transporters.[2][3][4]
Chemistry[]
Oxaprotiline is a racemic compound composed of two isomers, R(−)- or levo- oxaprotiline (levoprotiline; CGP-12,103-A), and S(+)- or dextro- oxaprotiline (dextroprotiline; CGP-12,104-A). Both enantiomers are active, with the levo- form acting as an antihistamine and the dextro- form having an additional pharmacology (see above), but with both unexpectedly still retaining antidepressant effects.[6]
See also[]
Maprotiline
References[]
^Giedke H, Gaertner H, Breyer-Pfaff U, Rein W, Axmann D (1986). "Amitriptyline and oxaprotiline in the treatment of hospitalized depressive patients. Clinical aspects, psychophysiology, and drug plasma levels". European Archives of Psychiatry and Neurological Sciences. 235 (6): 329–338. doi:10.1007/bf00381001. PMID3527706. S2CID24152419.
^ abcdeWaldmeier PC, Baumann PA, Hauser K, Maitre L, Storni A (June 1982). "Oxaprotiline, a noradrenaline uptake inhibitor with an active and an inactive enantiomer". Biochemical Pharmacology. 31 (12): 2169–76. doi:10.1016/0006-2952(82)90510-X. PMID7115436.
^ abReimann IW, Firkusny L, Antonin KH, Bieck PR (1993). "Oxaprotiline: enantioselective noradrenaline uptake inhibition indicated by intravenous amine pressor tests but not alpha 2-adrenoceptor binding to intact platelets in man". European Journal of Clinical Pharmacology. 44 (1): 93–5. doi:10.1007/BF00315288. PMID8382162. S2CID22691825.
^ abNoguchi S, Inukai T, Kuno T, Tanaka C (June 1992). "The suppression of olfactory bulbectomy-induced muricide by antidepressants and antihistamines via histamine H1 receptor blocking". Physiology & Behavior. 51 (6): 1123–7. doi:10.1016/0031-9384(92)90297-F. PMID1353628. S2CID29562845.
^Noguchi S, Fukuda Y, Inukai T (May 1992). "Possible contributory role of the central histaminergic system in the forced swimming model". Arzneimittel-Forschung. 42 (5): 611–3. PMID1530672.