438-60-8

Usage

Uses

Used in Pharmaceutical Industry:
Protriptyline is used as an antidepressant for treating severe depression. It works by modulating the levels of certain neurotransmitters in the brain, such as norepinephrine and serotonin, which are involved in regulating mood. The exact mechanism of action is not fully understood, but it is known to be effective in alleviating depressive symptoms and improving the overall quality of life for patients suffering from severe depression.

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–C11 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) [33–38].

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.

InChI:InChI=1S/C19H21N/c1-20-14-6-11-19-17-9-4-2-7-15(17)12-13-16-8-3-5-10-18(16)19/h2-5,7-10,12-13,19-20H,6,11,14H2,1H3

Upstream product

• 521-80-2 N,N-dimethyl-3-(5H-dibenzo[a,d]cyclohepten-5-yl)-propylamine 
• 19071-94-4 C₁₉H₂₀O₃S 
• 74-89-5 methylamine 
• 18506-04-2 5-chloro-5H-dibenzo[a,d]cycloheptene 
• 18029-54-4 5-[3-(N,N-dimethylamino)propyl]-5H-dibenzo[a,d]cyclohepten-5-ol 

Downstream Products

• 108141-75-9 5-Methyl-2-cyclohepten-5-yl)-propylamino>-1,4-benzochinon 
• 108141-79-3 6-Methyl-2-cyclohepten-5-yl)-propylamino>-1,4-benzochinon 
• 27462-57-3 10-Hydroxyprotriptyline 
• 29785-65-7 10,11-Dihydroprotriptyline diol 
• 108141-84-0 5-Methyl-2-<3-(5H-dibenzocyclohepten-5-yl)-propylamino>-1,4-benzochinon 

Relevant academic research and scientific papers

PROCESS FOR PREPARATION OF 5H-DIBENZO[A,D] CYCLOHEPTENE DERIVATIVES

A process for preparation of protriptyline hydrochloride from 5-dihydrobenzocycloheptatriene of formula (1) by coupling with chloropropyl alcohol in the presence of excess n-butyl Lithium in tetrahydrofuran under inert atmosphere, followed by preparation of mesylate derivative of formula (3) and finally the nucleophilic displacement of the mesylate group by reacting methylamine solution in methanol to give protriptyline free base of the formula (4). Also the present process reveals the hydrochloride salt formation and purification of the same to give pure pharmaceutical grade protriptyline hydrochloride with impurities less than 0.1% w/w.

5H Dibenzo[a,d]cycloheptene derivatives

Compounds of 5H dibenzo[a,d]-cycloheptenes and 10,11-dihydro-5H-dibenzo[a,d]cycloheptenes which are substituted at their 5-carbon atom with an N-cyanoaminopropyl or an N-cyanoaminopropylidene radical.