Isoprenaline
| Evidence Level: L3 | Predicted Indications: 10 |
Table of Contents
Isoprenaline: A Historical Bronchodilator Revisited for Bronchial Disease
One-Sentence Summary
Isoprenaline (DrugBank DB01064) currently has no recorded India (CDSCO) marketing authorization and no documented original indication or mechanism-of-action entry in this evidence pack. Among the 10 disease candidates predicted by TxGNN, Bronchial Disease stands out as the only one backed by substantive evidence — 1 clinical trial hit (excluded on relevance review) and 20 supporting publications, largely comparative studies from the 1960s–1980s documenting isoprenaline’s use as a bronchodilator in asthma.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not recorded (no India license data; MOA also unavailable — see Data Gaps DG001/DG002) |
| Predicted New Indication | Bronchial Disease |
| TxGNN Prediction Score | 99.77% (rank 4538 of candidate pool) |
| Evidence Level | L3 |
| India Market Status | Not Marketed |
| Number of Registrations | 0 |
| Recommended Decision | Proceed with Guardrails |
Why is This Prediction Reasonable?
Detailed mechanism-of-action data for Isoprenaline is currently unavailable in this pack (Data Gap DG002). However, the supporting literature is unambiguous on pharmacology: Isoprenaline is a non-selective β1/β2-adrenergic receptor agonist. β2 activation drives bronchial smooth-muscle relaxation, which made it a standard bronchodilator for asthma and bronchospasm through the 1960s–1970s, before selective β2-agonists (e.g., salbutamol) largely replaced it.
Because of this, “Bronchial Disease” is less a novel repurposing signal and more a re-confirmation of a well-established historical indication — multiple comparative studies in the evidence set directly pit isoprenaline against salbutamol and orciprenaline on spirometry, blood-gas, and cardiorespiratory endpoints in asthmatic patients.
The trade-off that keeps this from being a clean “Go”: isoprenaline’s non-selective β1 activity produces tachycardia and blood-pressure changes that selective agents avoid, and the literature also documents beta-adrenergic tachyphylaxis with repeated use. This is precisely why modern practice moved away from it, and why any revival requires explicit safety guardrails rather than a straightforward reintroduction.
Clinical Trial Evidence
No clinical trials directly testing Isoprenaline in Bronchial Disease are currently registered. The search returned one trial by indication-matching only — NCT02230332 (Phase 2/3, Completed, N=78, “Proof of Concept Study of Alendronate for Asthma”) — but this was excluded: the test drug is Alendronate, not Isoprenaline, and the pack’s own relevance grading (Grade C) confirms no direct link to this repurposing hypothesis.
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 5440568 | 1970 | Comparative study | British Medical Journal | Salbutamol and isoprenaline both significantly reduced airway obstruction in asthma; isoprenaline caused tachycardia and a small fall in arterial oxygen tension, salbutamol did not |
| 5411446 | 1970 | Comparative study | British Medical Journal | Isoprenaline and salbutamol were equipotent bronchodilators, but isoprenaline caused a greater rise in pulse rate and blood pressure change |
| 663881 | 1978 | Comparative study | Thorax | In 19 patients with airway obstruction, dilator response to inhaled isoprenaline correlated significantly with constrictor response to histamine (r=+0.83) |
| 5968121 | 1966 | Comparative study | Thorax | Compared effects of norepinephrine and isoprenaline on airway resistance in chronic bronchial obstruction |
| 14019931 | 1962 | Comparative study | Lancet | Early study of atropine methonitrate and isoprenaline combined use in bronchial asthma |
| 471074 | 1979 | Comparative study (animal) | Naunyn-Schmiedeberg’s Arch Pharmacol | In guinea pigs, isoprenaline was ~2,600× more potent than sodium nitroprusside as an anti-asthmatic bronchodilator |
| 201045 | 1977 | Comparative study | Thorax | Factorial study (n=38) of isoprenaline plus aminophylline in asthma — relevant drug-interaction/efficacy data |
| 5565461 | 1971 | Comparative study | Archives of Disease in Childhood | In 12 asthmatic children, isoprenaline, orciprenaline, and salbutamol relieved bronchoconstriction similarly, but isoprenaline produced the largest heart-rate (+29%) and blood-pressure rise — pediatric cardiac safety signal |
| 90979 | 1979 | Not yet classified | Lancet | Titled “Fatal asthma” — a historical safety signal relevant to beta-agonist use in asthma; abstract not available in this pack |
| 6128356 | 1982 | Review | J Allergy Clin Immunol | Review of beta-adrenergic tachyphylaxis, relevant to repeated isoprenaline dosing |
India Market Information
No CDSCO marketing authorizations for Isoprenaline are currently on record (0 registrations; market status: Not Marketed). Establishing a repurposing pathway in India would require a new registration, not a label extension.
Safety Considerations
- Drug Interactions: 367 total interactions on record. The sample provided includes one Major-level interaction (Dolasetron) and several Moderate-level interactions relevant to a bronchial-disease population, including epinephrine, clarithromycin, and multiple antidiabetic agents (acarbose, alogliptin, canagliflozin, dapagliflozin, empagliflozin, dulaglutide, albiglutide). Most remaining listed interactions (corticosteroids: hydrocortisone, triamcinolone, dexamethasone, beclomethasone, betamethasone, budesonide) are Minor.
Key warnings and contraindications are not available in this pack (Data Gap DG001) — please refer to the package insert once available.
Conclusion and Next Steps
Decision: Proceed with Guardrails
Rationale: Multiple mid-20th-century comparative studies consistently support isoprenaline’s bronchodilator efficacy in asthma/bronchial disease, and its β1/β2-agonist mechanism is well understood — but the same literature documents cardiac stimulation, tachyphylaxis, and at least one historical “fatal asthma” safety signal tied to non-selective beta-agonist use, and no completed trial in this pack tested isoprenaline itself against a placebo-controlled modern endpoint.
To proceed, the following is needed:
- TFDA/CDSCO-equivalent package insert warnings and contraindications (Data Gap DG001, Blocking)
- Confirmed DrugBank mechanism-of-action entry (Data Gap DG002, High)
- Formal review of the “Fatal asthma” (PMID 90979) safety signal and modern cardiac-risk context relative to selective β2-agonists
- A defined India registration pathway, since the drug currently holds zero CDSCO licenses
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.