Oxaprotiline Explained

Oxaprotiline (developmental code name C 49-802 BDA), also known as hydroxymaprotiline, is a norepinephrine reuptake inhibitor belonging to the tetracyclic antidepressant (TeCA) family and is related to maprotiline. Though investigated as an antidepressant,^[1] it was never marketed.

Pharmacology

Dextroprotiline acts as a potent norepinephrine reuptake inhibitor^{[2] [3]} and H₁ receptor antagonist,^[4] as well as a very weak α₁-adrenergic receptor antagonist.^[5] It has negligible affinity for the serotonin transporter, dopamine transporter, α₂-adrenergic receptor, and muscarinic acetylcholine receptors. 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 selective H₁ receptor antagonist, with no affinity for adrenaline, dopamine, muscarinic acetylcholine, or serotonin receptors, or any of the monoamine transporters.

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

Notes and References

1. Giedke H, Gaertner H, Breyer-Pfaff U, Rein W, Axmann D . Amitriptyline and oxaprotiline in the treatment of hospitalized depressive patients. Clinical aspects, psychophysiology, and drug plasma levels . European Archives of Psychiatry and Neurological Sciences . 1986 . 235 . 6 . 329–338 . 3527706 . 10.1007/bf00381001. 24152419 .
2. Waldmeier PC, Baumann PA, Hauser K, Maitre L, Storni A . Oxaprotiline, a noradrenaline uptake inhibitor with an active and an inactive enantiomer . . 31 . 12 . 2169–76 . June 1982 . 7115436 . 10.1016/0006-2952(82)90510-X.
3. Reimann IW, Firkusny L, Antonin KH, Bieck PR . 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 . 1993 . 8382162 . 10.1007/BF00315288. 22691825 .
4. Noguchi S, Inukai T, Kuno T, Tanaka C . The suppression of olfactory bulbectomy-induced muricide by antidepressants and antihistamines via histamine H1 receptor blocking . Physiology & Behavior . 51 . 6 . 1123–7 . June 1992 . 1353628 . 10.1016/0031-9384(92)90297-F. 29562845 .
5. Richelson E, Nelson A . Antagonism by antidepressants of neurotransmitter receptors of normal human brain in vitro . The Journal of Pharmacology and Experimental Therapeutics . 230 . 1 . 94–102 . July 1984 . 6086881 .
6. Noguchi S, Fukuda Y, Inukai T . Possible contributory role of the central histaminergic system in the forced swimming model . Arzneimittel-Forschung . 42 . 5 . 611–3 . May 1992 . 1530672 .