Oxaprotiline

Pharmacology

Dextroprotiline acts as a potent norepinephrine reuptake inhibitor and H1 receptor antagonist, as well as a very weak α1-adrenergic receptor antagonist. 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.

References

References

1. (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.
2. (June 1982). "Oxaprotiline, a noradrenaline uptake inhibitor with an active and an inactive enantiomer". [[Biochemical Pharmacology (journal).
3. (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.
4. (June 1992). "The suppression of olfactory bulbectomy-induced muricide by antidepressants and antihistamines via histamine H1 receptor blocking". Physiology & Behavior.
5. (July 1984). "Antagonism by antidepressants of neurotransmitter receptors of normal human brain in vitro". The Journal of Pharmacology and Experimental Therapeutics.
6. (May 1992). "Possible contributory role of the central histaminergic system in the forced swimming model". Arzneimittel-Forschung.