THERAPY DOSSIER · th-9d93054d812c

Amitriptyline, clomipramine and desipramine, with and without the selective iNOS inhibitor aminoguanidine

Drug · Tricyclic antidepressant; direct inhibitor of the serotonin transporter (CHEMBL228) and norepinephrine transporter (CHEMBL222); ATC N06AA09; black box warning TRUE. Only amitriptyline resolved; clomipramine, desipramine and aminoguanidine not separately queried this run

No trauma translation Suggest a correction

This record is classified as “NO TRAUMA TRANSLATION”. Read the indication and notes below for the specific context.

Evidence & regulatory context

Mechanism: Tricyclic antidepressant; direct inhibitor of the serotonin transporter (CHEMBL228) and norepinephrine transporter (CHEMBL222); ATC N06AA09; black box warning TRUE. Only amitriptyline resolved; clomipramine, desipramine and aminoguanidine not separately queried this run
Target: CHEMBL228 (SERT); CHEMBL222 (NET)
Injury models: Other
Reported indication: Major depressive disorder (tricyclic antidepressant; approved 1961); widely used off-label for neuropathic/chronic pain
First approval: 1961
Development stage: Approved antidepressant; topical burn/neuropathy (acute-injury) formulations investigational
ChEMBL record: CHEMBL629 ↗
ChEMBL max phase: 4 / 4 (development scale, not regulatory approval)
Synonyms: Amitriptilina; Laroxyl; Proheptadiene; Triptanol; amitriptyline hydrochloride CHEMBL1200964 (Elavil, Tryptizol, Saroten)
Note: Not recorded

Clinical trials 15

2 linked trials carry an injury-indication flag. These flags support record-level exploration and sit alongside the stringent aggregate counts described in Methods.

NCT00006427 ↗Injury indicationPHASE4completed

Management of Chronic Pain in Persons With Amputation (Amitriptyline)

Amputation, Traumatic · Pain · Postoperative Pain

Enrolment: 125 · Results not recorded

NCT07716722 ↗Injury indicationPHASE1not yet recruiting

Pilot studies blocking injury-induced microvesicle particle release in skin using topical amitriptyline (thermal burn)

Thermal Burn

Enrolment: 50 · Results not recorded

NCT04725383 ↗PHASE3terminated

Amitriptyline for Repetitive Behaviors in Children and Adolescents With Autism

Autism Spectrum Disorder

Enrolment: 1 · Results not recorded

NCT01357031 ↗PHASE3completed

Melatonin versus amitriptyline versus placebo in preventive treatment of migraine

Migraine

Enrolment: 192 · Results not recorded

NCT01347684 ↗PHASE3withdrawn

Two treatment strategies for tension-type headache (standard care using current drugs including amitriptyline)

Tension-type Headache

Enrolment: 0 · Results not recorded

NCT07296770 ↗PHASE3not yet recruiting

AI-driven approach to optimise patient selection for a transitional pain service (pharmacologic pain management)

Postsurgical Pain, Chronic

Enrolment: 126 · Results not recorded

NCT00210860 ↗PHASE3completed

Open-label topiramate for migraine prophylaxis, extension to CAPSS-277

Migraine

Enrolment: 142 · Results not recorded

NCT02041455 ↗PHASE2/PHASE3unknown

Immune-pineal Axis in Fibromyalgia: Melatonin and/or Amitriptyline

Fibromyalgia

Enrolment: 66 · Results not recorded

NCT03591458 ↗PHASE2terminated

Amitriptyline for Improving Hypoglycemia Course and Recognition

Type 1 Diabetes Mellitus · Hypoglycemia Unawareness

Enrolment: 2 · Results not recorded

NCT01014520 ↗PHASE2unknown

Single-dose pre-emptive gabapentin or amitriptyline on postoperative pain in lumbar laminectomy and discectomy

Herniated Disc · Intervertebral Disc Displacement

Enrolment: 120 · Results not recorded

NCT05593614 ↗PHASE2active not recruiting

ATX01 (topical amitriptyline hydrochloride 10% and 15%) in chemotherapy-induced peripheral neuropathy

Chemotherapy-induced Peripheral Neuropathy

Enrolment: 276 · Results not recorded

NCT06091553 ↗PHASE2unknown

Duloxetine augmented with gabapentin or amitriptyline versus duloxetine alone in chemotherapy-induced neuropathy

Neuropathy in Cancer Patients

Enrolment: 160 · Results not recorded

NCT01306708 ↗PHASE2completed

Amitriptyline versus nimesulide with nervous blockade in acute idiopathic adhesive capsulitis

Adhesive Capsulitis

Enrolment: 34 · Results not recorded

NCT03646526 ↗PHASE1completed

Bioavailability Study of Amitriptyline Hydrochloride Tablets

Depressive Disorder

Enrolment: 60 · Results not recorded

NCT02256878 ↗PHASE1completed

Effect of BIRT 2584 XX on the pharmacokinetics of amitriptyline and nortriptyline in healthy subjects

Healthy

Enrolment: 24 · Results not recorded

Preclinical evidence 2

2 studies reported at therapy level; 2 evidence entries itemised.

PMID 22584260 ↗2012Mixed findings

Comparative evaluation of the effect of tricyclic antidepressants on inducible nitric oxide synthase expression in neuropathic pain model.

RatOtherWistarmaleIntraperitonealAcute administration after sciatic nerve injury

Model: Chronic constriction injury of the sciatic nerve producing neuropathic pain

Amitriptyline and clomipramine produced antinociceptive effects after chronic constriction injury whereas desipramine did not. The effect of amitriptyline, but not clomipramine, was augmented by aminoguanidine, and amitriptyline inhibited iNOS mRNA and protein expression in cerebellum and hippocamp…

Extraction: extract · Supplied extraction confidence: 0.65. Machine-extracted fields require source verification.

PMID 22720761 ↗2012Reported benefit

Pretreatment with intrathecal amitriptyline potentiates anti-hyperalgesic effects of post-injury intra-peritoneal amitriptyline following spinal nerve ligation.

RatOtherSprague-DawleyMalen = 96 rats, n = 24 per group across four groups, with n = 4 to…Intraperitoneal, and intrathecal via the L4-5 intervertebral spaceIntraperitoneal 12.5 mg/kg (50 mg/mL in saline); intratheca…Intrathecal dose given as pretreatment with surgery performed 10 minutes later;…

Model: Left L5 spinal nerve ligation with 6-0 Dexon after removal of the left L6 transverse process, producing neuropathic pain

Intraperitoneal amitriptyline alone reduced thermal hypersensitivity to postoperative day 7, reversed Nav1.8 downregulation and reduced microglial activation by day 14. Adding intrathecal pretreatment extended the thermal benefit, attenuated mechanical hypersensitivity at day 7, reduced Nav1.3 upre…

Extraction: extract · Supplied extraction confidence: 0.9. Machine-extracted fields require source verification.

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