Uses
Protriptyline is a powerful antidepressant, the mechanism of action of which is not
known. It is not a MAO inhibitor and does not stimulate the CNS. It begins to act much
faster and acts much longer than imipramine or amitriptyline. Protriptyline does not possess sedative tranquilizing properties. It is used in clinical conditions for treating severe
depression.
Definition
ChEBI: Protriptyline is a carbotricyclic compound. It has a role as an antidepressant. It derives from a hydride of a dibenzo[a,d][7]annulene.
brand name
Vivactil (Odyssey).
Mechanism of action
Protriptyline exhibits high selectivity for the NE transporter, but with less potency than desipramine. Its
mechanism of action is similar to that of desipramine. Minimal effect on 5-HT reuptake has been observed.
Synthesis
Protriptyline, N-methyl-5-H-dibenzo[a,d]cyclohepten-5-propylamine (7.1.22),
differs from all of the drugs described above in that there is present a double bond at the
C10¨CC11 position of the central 7-membered ring of the tricyclic part of the molecule. At
the same time, a free electron pair on C5 belonging to either a nitrogen atom or an exocyclic double bond are excluded, which undoubtedly changes both the architecture of the
whole molecule as well as, the collocation of pharmacophore groups.
Protriptyline is synthesized by alkylation of 5-H-dibenzo[a,d]cycloheptene with 3-(Nphormyl-N-methylamino)propylchloride (7.1.20), which is synthesized from compound
(7.1.19). The resulting intermediate product (7.1.21) undergoes alkaline hydrolysis, which
leads to the formation of protriptyline (7.1.21) [33¨C38].
Metabolism
Protriptyline is a dibenzocycloheptriene TCA that differs from the other tricyclics by having an unsaturated
ethylene bridge joining the two aromatic rings and a secondary aminopropyl side chain.
Protriptyline is completely absorbed from the GI tract and slowly eliminated. Metabolism data are limited for protriptyline, but it is most likely to be metabolized via the same
pathways as the other TCAs are. Very little drug is excreted in the feces via the bile.
