Protriptyline is a tricyclic antidepressant.1 It binds to the norepinephrine and serotonin (5-HT) transporters with Kd values of 1.41 and 19.6 nM, respectively. Protriptyline also binds to histamine H1, muscarinic acetylcholine, and α1-adrenergic receptors (Kds = 25, 25, and 130 nM, respectively).2 It inhibits norepinephrine uptake into rat whole brain and hypothalamic synaptosomes (IC50s = 12 and 0.55 μM, respectively) and 5-HT uptake into rat whole brain synaptosomes (IC50 = 5.5 μM).3 Protriptyline (1 mg/kg, i.v.) inhibits food-induced cataplexy in narcoleptic dogs.4 Formulations containing protriptyline have been used in the treatment of depression.
1.Tatsumi, M., Groshan, K., Blakely, R.D., et al.Pharmacological profile of antidepressants and related compounds at human monoamine transportersEur. J. Pharmacol.340(2-3)249-258(1997) 2.Richelson, E., and Nelson, A.Antagonism by antidepressants of neurotransmitter receptors of normal human brain in vitroJ. Pharmacol. Exp. Ther.230(1)94-102(1984) 3.Schacht, U., and Heptner, W.Effect of nomifensine (HOE 984), a new antidepressant, on uptake of noradrenaline and serotonin and on release of noradrenaline in rat brain synaptosomesBiochem. Pharmacol.23(24)3413-3422(1974) 4.Foutz, A.S., Delashaw, J.B., Jr., Guilleminault, C., et al.Monoaminergic mechanisms and experimental cataplexyAnn. Neurol.10(4)369-376(1981)