Drug Database
TH

theophylline (Contiphyllin / Diffumal 24)

✓ Approved

Lindopharm · ADORA1 · Small Molecule

What is theophylline?

theophylline is a small molecule developed by Lindopharm. It is approved for therapeutic indications via oral (po).

Drug Profile

Brand NamesContiphyllin, Diffumal 24
CompanyLindopharm
Drug ClassSmall Molecule
Molecular TargetADORA1, ADORA2A
RouteOral (PO)
StatusApproved
Sources: ClinicalTrials.gov, Lindopharm

Mechanism of Action

Molecular Targets

theophylline acts on 2 molecular targets:

ADORA1adenosine A1 receptor (RDC7)
ADORA2Aadenosine A2a receptor (A2aR, RDC8)
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Therapeutic Indications

theophylline is developed for 1 unique indication across 1 therapeutic area.

Therapeutic AreaConditionPhase
Respiratory, thoracic and mediastinal disordersAsthma✓ Approved

Related Research Articles

PubMedMolecules (Basel, Switzerland)2026-10-16

Evaluation of Interleukin-8 (IL-8) Expression in Human Aortic Endothelial Cells (HAECs) and Antioxidant Activity of Isolated Compounds from the Endemic Hawaiian Plant Pipturus albidus (Māmaki).

Meesakul Pornphimon P, Kim Kyung Ah KA, Si Yaru Y, Kuroki Yutaka Y et al.

Pipturus albidus (commonly known as māmaki) is an endemic Hawaiian plant traditionally consumed as a medicinal herbal tea; however, its comprehensive potential for phytochemical composition and biological activities remains underexplored. In this study, we present the first comprehensive phytochemical characterization of the ethanol extract of P. albidus, identifying twelve compounds through chromatographic and spectroscopic analyses. The isolated compounds were subjected to a series of antioxidant assays, including 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging, ferric reducing antioxidant power (FRAP), and oxygen radical absorbance capacity (ORAC). Cinchonain Ia (2), vitexin (6), and (7S,8R)-dihydrodehydro diconiferyl alcohol (11) demonstrated strong free radical-scavenging and reducing capacities. Evaluation of Interleukin-8 (IL-8) expression in TNF-α-stimulated human aortic endothelial cells (HAECs) revealed that catechin-(7,8-bc)-4a-(3,4-dihydroxyphenyl)-dihydro-2(3H)-pyranone (3) and trans-ferulic acid (9) significantly increased IL-8 mRNA expression (p < 0.05), indicating potential pro-inflammatory effects of these isolated constituents. In contrast, neither the crude extract (PE) nor vitexin (6) produced a statistically significant difference in IL-8 mRNA levels compared to the TNF-α control (p < 0.05). Quantitative LC-MS/MS analysis confirmed that caffeine, theobromine, theophylline, and EGCG were below the limit of detection in P. albidus leaf extracts, indicating that P. albidus possesses a phytochemical constituent distinct from that of green tea. In summary, P. albidus leaves contain unique phytochemicals with cell-free antioxidant activity, while cell-based assays indicate potential pro-inflammatory risks for compounds 3 and 9 and no significant anti-inflammatory suppression by PE or vitexin (6).

PMID 42883215
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PubMedFood and chemical toxicology : an international journal published for the British Industrial Biological Research Association2026-10-15

Evaluating the biological effects of caffeine-related compounds methylliberine and theacrine by integrated in silico and in vitro new approach methods (NAMs).

Santillo Michael F MF, Sprando Robert L RL, Yourick Jeffrey J JJ

Methylliberine (1,O2,7,9-tetramethyluric acid; 1,2,7,9-MU) and theacrine (1,3,7,9-tetramethyluric acid; 1,3,7,9-MU) are purine alkaloids found in a variety of botanicals and products marketed as dietary supplements. Despite their widespread use, extensive data on their human health effects are lacking. Therefore, methylliberine and theacrine were profiled using multiple new approach methods (NAMs): in silico metabolite predictions, in silico blood-brain barrier (BBB) permeability predictions, and in vitro assays for adenosine receptor binding (A1, A2A), functional activity (A2A), cytochrome P450 inhibition (CYP1A2), and phosphodiesterase inhibition (PDE3A, PDE4B, PDE4D). Like caffeine, methylliberine and theacrine were predicted to be metabolized via desmethylation by multiple in silico models. In silico predictions and cluster analysis also suggested that methylliberine and theacrine may permeate the BBB like caffeine. In vitro assays revealed that methylliberine and its metabolite 1,2,9-MU were CYP1A2 inhibitors (IC50, 9.6 and 27 μM, respectively) that agreed with clinical observations and could lead to interactions with drugs and xenobiotics. Both methylliberine and theacrine were A2A receptor antagonists, suggesting a potential for stimulant effects, although their potencies (52-62% inhibition at 100 μM) were weaker than theophylline, paraxanthine, and caffeine (IC50, 4.9-23.3 μM). Overall, this study highlights integration of multiple NAMs for profiling two purine alkaloids relevant to human health.

PMID 42880479
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PubMedArchiv der Pharmazie2026-10-15

Synthesis of Some New Xanthine Derivatives and Evaluation of DPP IV Inhibitory Activities.

Akgün Erol E, Yurttaş Leyla L, Kaleli Sevde Nur Biltekin SNB, Osmaniye Derya D et al.

Dipeptidyl peptidase IV (DPP IV) inhibition prolongs incretin activity and represents an established therapeutic strategy for the management of type 2 diabetes mellitus. To investigate the underexplored combination of benzyl groups at the N7 position and a piperazine-linked arylthiazole moiety at the C8 position of the xanthine scaffold, 15 novel compounds (6a-6o) were synthesised. The synthetic route involved bromination at the C8 position of theophylline, introduction of benzyl groups at the N7 position, replacement of the bromine atom at the C8 position with piperazine, and subsequent cyclocondensation with phenacyl thiocyanate derivatives. All final compounds were characterised by 1H and 13C NMR spectroscopy, high-resolution accurate-mass mass spectrometry, and analytical HPLC. All derivatives inhibited DPP IV in the low-nanomolar range, with compounds 6c and 6b showing the highest activities, with IC50 values of 3.95 ± 0.53 and 4.04 ± 0.65 nM, respectively. NIH3T3 cytotoxicity IC50 values ranged from 28.52 to 397.63 µM, indicating substantial preliminary concentration margins relative to DPP IV inhibition. Molecular docking, 100 ns molecular dynamics simulations, interaction-fingerprint analyses and trajectory-based MM/PBSA calculations supported persistent interactions with key DPP IV active-site residues. These results identify the synthesised derivatives, particularly 6b and 6c, as promising lead structures for further optimisation.

PMID 42876006
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PubMedPloS one2026-10-08

A modular toolkit for theophylline-dependent synthetic auxotrophs via riboswitch-gated essential genes.

Gonzalez-Lopez Carlos C, Overly Adrian A, Singh Saahil S, Huang Charlie C et al.

Synthetic auxotrophs are a useful means for developing genetically encoded biocontainment systems. Current methods for developing synthetic auxotrophs are complicated or expensive, limiting access and adoption of biocontainment technologies. To address this gap, we developed a simple and modular platform for creating synthetic auxotrophs based on ligand-dependent translational gating of essential genes. By inserting a theophylline-responsive riboswitch upstream of essential genes in Escherichia coli, we created strains whose viability depends on the presence of theophylline. We systematically applied this approach to 29 essential genes, obtained ligand-dependent growth phenotypes for 19 targets, and found that 18 of these essential genes yielded stringent live-die synthetic auxotrophs. These strains exhibited robust theophylline dependence with escape frequencies ranging from 1 × 10-5 to 1 × 10-6 (most below limit of detection). Our modular design allows for the rapid (<1 week), low-cost, and reliable generation of synthetic auxotrophs. This work introduces ligand-dependent translational control as a new mechanism for engineering synthetic auxotrophy and provides an accessible platform that expands the biocontainment toolkit.

PMID 42848817
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PubMedBMC psychiatry2026-10-08

Psychiatric, anesthetic, and procedural characteristics of modified electroconvulsive therapy courses in adolescents treated in a tertiary child and adolescent psychiatry service: a 15-year retrospective cohort study.

Alnak Alper A, Oflezer Ceyhan C

Evidence on electroconvulsive therapy (ECT) in adolescents is largely retrospective and rarely reports psychiatric outcomes together with anesthetic and procedural characteristics. We characterized modified ECT courses in a tertiary child and adolescent psychiatry service. This retrospective cohort included adolescents aged 13-18 years treated with modified ECT from 2010 to 2025; the ECT course was the unit of analysis. Illness severity was rated with the Clinical Global Impression-Severity (CGI-S) scale at admission and discharge. The primary outcome was a composite of any documented hemodynamic event, prolonged seizure, or recovery/behavioral event; short or absent seizures were analyzed separately as a technical seizure-adequacy outcome. Logistic models used standard errors clustered by patient. Among 156 ECT courses in 150 adolescents (1,465 sessions), diagnoses were schizophrenia spectrum (46.2%), bipolar spectrum (23.1%), neurodevelopmental (18.6%), and depressive disorders (12.2%). Median CGI-S decreased from 5.0 at admission to 3.0 at discharge, with a study-defined decrease of at least 2 points in 152 courses (97.4%) and a discharge CGI-S of 2 or less in 60 (38.5%). The primary composite event occurred in 63 courses (40.4%), involving one event domain in 49 (31.4%) and two or more in 14 (9.0%). Short or absent seizures occurred in 42 courses (26.9%); theophylline use was associated with higher odds of this outcome, most plausibly reflecting confounding by indication. Estimates for age, bipolar spectrum disorder, and succinylcholine dose were imprecise and hypothesis-generating. In this severe tertiary cohort, ECT-centered inpatient care was associated with substantial within-course global improvement, and acute course-level events were common but usually confined to a single domain. Acute anesthesia- or procedure-related events and technical seizure adequacy should be reported separately, and exploratory dose or medication associations should not be interpreted causally.

PMID 42844607
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PubMedResearch in pharmaceutical sciences2026-10-06

Synthesis, in vitro and in silico evaluation of quinazoline and triazoloquinazoline derivatives as PDE7A inhibitors.

El-Malah Afaf A AA, Gineinah Magdy M MM, Khayat Maan T MT, Neamatallah Thikryat T et al.

Phosphodiesterase 7A (PDE7A) is an attractive therapeutic target for the treatment of inflammatory, autoimmune, and neurodegenerative disorders through modulation of intracellular cAMP levels. However, the development of highly potent and selective PDE7A inhibitors remains challenging. This study aimed to design, synthesize, and evaluate 2-chloroquinazoline and fused 1,2,4-triazolo[4,3-c]quinazoline derivatives as potential PDE7A inhibitors, supported by molecular docking, molecular dynamics simulations, and in silico toxicity prediction. A series of 2-chloroquinazoline derivatives 4a-f and their fused 1,2,4-triazolo[4,3-c]quinazoline counterparts 5a-d were synthesized as phosphodiesterase 7A (PDE7A) inhibitors. The synthesized compounds were evaluated for their in vitro inhibitory activity against phosphodiesterase 7A (PDE7A) and were compared with theophylline and BRL50481, a selective PDE7 inhibitor. All compounds demonstrated enzyme inhibition ranging from 0.062 to 1.35 μM;. Derivatives 5c and 5d exhibited the most potent inhibitory effects, with IC50 values of 0.076 and 0.062 μM;, respectively, and were not significantly different from BRL50481 (IC50 = 0.034 μM;), while being significantly more potent than theophylline (IC50 = 0.539 μM;). These compounds, together with 4c and 5a, showed superior inhibitory activity compared with theophylline. Molecular docking and molecular dynamics studies were performed to investigate binding interactions and stability within the PDE7A active site. Compounds 5c and 5d displayed high binding affinity and stability within the active site. Their interactions with key amino acid residues support their potential as effective PDE7A inhibitors. Predicted toxicity data indicated a favorable safety profile across 30 toxicity endpoints, supporting their further development.

PMID 42836184
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