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enalapril maleate + HCTZ (Vasoretic / Vaseretic / Renidur)

✓ Approved

Merck & Co. · ACE · Small Molecule

What is enalapril maleate + HCTZ?

enalapril maleate + HCTZ is a small molecule developed by Merck & Co.. It is approved for therapeutic indications via oral (po).

Drug Profile

Brand NamesVasoretic, Vaseretic, Renidur
CompanyMerck & Co.
Drug ClassSmall Molecule
Molecular TargetACE, SLC12A3
RouteOral (PO)
StatusApproved
Sources: ClinicalTrials.gov, Merck & Co.

Mechanism of Action

Molecular Targets

enalapril maleate + HCTZ acts on 2 molecular targets:

ACEangiotensin I converting enzyme (DCP1, ACE1)
SLC12A3solute carrier family 12 member 3 (NCCT, NCC)
Want deeper analysis?Noah AI can explain complex mechanisms and compare to similar drugs.

Therapeutic Indications

enalapril maleate + HCTZ is developed for 1 unique indication across 1 therapeutic area.

Therapeutic AreaConditionPhase
Vascular disordersHypertension✓ Approved

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Managing multi-resistant German cockroaches with dinotefuran: toxicity, bait performance, secondary transfer, and residual effectiveness.

Huang Chun-Ting CT, Chen Mei-Er ME, Lee Chow-Yang CY, Neoh Kok-Boon KB

The German cockroach, Blattella germanica (Linnaeus), has evolved resistance to multiple insecticide classes, threatening the effectiveness of management programs. Although dinotefuran has become an alternative for cockroach management, its efficacy against field populations with documented resistance to multiple insecticide classes remains poorly understood. We evaluated dinotefuran susceptibility in 11 field populations from Taiwan and assessed the efficacy of commercial gel bait and residual spray formulations. Topical bioassays revealed reduced susceptibility in 8 populations at the 1× LD95 diagnostic dose, whereas only 2 exhibited reduced susceptibilities at the 3× LD95. Synergism assays demonstrated that piperonyl butoxide completely restored susceptibility in resistant populations, suggesting cytochrome P450 monooxygenases as the detoxification mechanism. Additional effects of S,S,S-tributyl phosphorotrithioate and diethyl maleate further suggested that esterases and glutathione-S-transferases also contributed to resistance in some populations. Despite reduced susceptibility in topical bioassays, the commercial dinotefuran gel bait remained highly effective against field populations. Its efficacy persisted after aging, and secondary toxicant transfer through necrophagy caused substantial additional mortality when alternative food was unavailable. Residual sprays induced rapid knockdown and high 24-h mortality in adult males, but efficacy declined with residue age, particularly against adult females after 14 days. These findings indicate that dinotefuran formulations remain useful for German cockroach management despite variation in susceptibility among field populations. Integrating dinotefuran bait with sanitation and rotating insecticides with different modes of action may improve control while helping to delay resistance evolution. Timely reapplication of residual dinotefuran spray is necessary to maintain satisfactory control.

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Polyurethane Toughened Polystyrene With In-Situ Compatibilization and Controlled Hierarchical Microphase Structure by "One-Pot" Cascade Radical and Step-Growth Polymerizations.

Wang Xinpeng X, Wang Guochen G, Zhao Dan D, Cao Han H et al.

The microphase structure of multicomponent and multiphase polymers plays a critical role in determining their properties. A one-pot strategy integrating radical and step-growth polymerizations is developed to prepare polyurethane (PU)/polystyrene (PS) alloy (PUS) with a high-impact polystyrene (HIPS)-like salami morphology. Di-(6-hydroxylhexyl) maleate (HMH) is introduced as a dual-role monomer to form PS-g-PU as a compatibilizer in situ. When dibutyltin dilaurate (DBTDL) was initially mixed with poly(tetramethylene glycol), HMH, 4,4'-methylenebis(phenyl isocyanate), and styrene, delaying benzoyl peroxide (BPO) addition allowed the PU particles (0.1∼0.3 µm) to aggregate into larger PU microdomains. In contrast, when BPO was initially mixed with the monomers, delaying DBTDL addition promoted the formation of PS-grafted HMH, followed by their incorporation into PU chains and forming a salami-like morphology. The optimized PUS exhibited a notched impact and tensile strengths of 10.1 kJ/m2 and 45.5 MPa, respectively (9.4 kJ/m2 and 30.9 MPa for commercial HIPS). This work provides a one-pot route for coupling chain-growth and step-growth polymerizations to prepare PUS with controlled phase structures and in-situ compatibilization.

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Antifibrinolytic Agent: Synthesis and Characterization of Cocrystal and Salts of Tranexamic Acid.

Dayo Owoyemi Bolaji C BC, Adehinmoye Adedamola E AE, Zeller Matthias M, de Araujo Gabriel L B GLB et al.

Tranexamic acid (TXA) is a potent antifibrinolytic agent with poor oral bioavailability (∼35-40%) due to its high polarity and zwitterionic nature, while physicochemical factors, including its structural instability, further hinder its absorption. In this study, the crystal engineering concept is applied to enhance the physicochemical properties of TXA through targeted structural modifications, resulting in the synthesis of pharmaceutically stable cocrystal and salt forms. The application of supramolecular synthon design, pK a rule, and structural geometry (molecular mimicry), resulted in the rational design, synthesis, and structural characterization of eight binary multicomponent forms of TXA: a TXA-adipate salt, monoclinic space group P2 1/n; a TXA-salicylate salt, monoclinic space group P2 1/n; a TXA-picolinate salt, monoclinic space group P2 1/c; a TXA-acetaminophen cocrystal hydrate, monoclinic space group P2 1; a TXA-malonate salt, orthorhombic space group Pbca; a TXA-maleate salt hydrate, monoclinic space group P2 1/c; a TXA-malate salt, monoclinic space group P2 1/c; and a TXA-citrate salt, triclinic space group P1̅ These multicomponent forms were obtained via different hydrogen bonding interactions, some of them charge-assisted (N-H···O, N+-H···O-, O-H···O, and O-H···O-) between NH2 and/or -OH groups of TXA and the carboxyl (-C-(O-)O) functional groups of the coformers. In the cocrystals, TXA exists as zwitterions (zero charge), whereas in the salts, it carries a positive charge due to the protonation of its carboxylic (-COOH) and ammonium (-NH3 +) groups. The NH3 + to COO- charge-assisted H-bond provides stabilization to both the coformer COO- as well as the TXA's NH3 +. Solid-state characterization using Raman and FT-Raman spectroscopy, thermal techniques (DSC), and X-ray diffraction analysis (powder and single-crystal XRD) supports and confirms the structural novelty. The superior stability profiles of the new TXA cocrystal and salts under standard conditions (40 °C ± 2 °C, 75% ± 5% RH) establish an improved structure-property profile compared to pure TXA.

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PubMedChemico-biological interactions2026-11-04

Effect of ursodeoxycholic acid on the pharmacokinetics of enalapril and its active metabolite enalaprilat in mice: Implications for transporter-mediated drug-drug interaction.

Subba Romit Kumar RK, Panthi Mamata M, Lee Su-Jin SJ, Park Se Yong SY et al.

Ursodeoxycholic acid (UDCA) has been reported to alter the expression of hepatic transporters, such as organic anion-transporting polypeptides (OATPs), and multidrug resistance-associated proteins (MRPs). This study investigated the pharmacokinetic interactions between UDCA and enalapril-a substrate of hepatic Oatp1a1 and Mrp2-and its active metabolite enalaprilat, a substrate of Mrp4 and organic anion transporter 3 (Oat3), in mice fed a 1% UDCA-diet for seven days. In UDCA-diet mice, hepatic Oatp1a1 and Oatp1b2 mRNA expression levels were significantly reduced, whereas Mrp4 expression was upregulated. Following an intravenous bolus of enalapril (2 mg/kg), UDCA-diet mice exhibited increased systemic exposure (AUC0-∞) and peak plasma concentration (Cmax) of enalapril, whereas the hepatic distribution and volume of distribution at steady state (Vss) declined. Consequently, the ratio of the area under the plasma concentration-time curve for enalaprilat to that for enalapril (AUCm/AUCp) decreased. Although the total area under the plasma concentration-time curve from time zero to infinity (AUC0-∞) for enalaprilat remained unchanged, Cmax increased. Furthermore, the renal clearance of enalaprilat decreased, potentially due to UDCA-mediated inhibition of renal Oat3. These findings demonstrate that high UDCA exposure alters the disposition of enalapril and enalaprilat by modulating hepatic and renal transporters, supporting the potential for transporter-associated drug interactions under elevated UDCA exposure.

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PubMedPharmaceutical development and technology2026-11-04

Potential use of cellulose nanocrystals as multifunctional excipient in chlorphenamine maleate nasal spray formulations.

Mariano Marcos M, Kearney Emma E, Ng Elray E, O'Dwyer Lorna L et al.

Nasal spray performance depends strongly on excipient properties, which govern plume formation, droplet size, and mucociliary retention. However, currently available excipients rarely combine these functionalities. In alignment with the FDA's PRIME initiative for excipient modernisation, we demonstrate that cellulose nanocrystals (CNCs) represent a promising class of multifunctional excipients. As a case study, we evaluated CNCs as multifunctional excipients in chlorphenamine maleate (CM) formulations. Samples containing up to 2 wt% CNC delivered uniform doses, tunable plume areas (30-61 cm2), and stable droplet sizes (d50 = 116-189 µm). Owing to their anisotropic shape, the nanoparticles exhibited shear-thinning behaviour with partial viscosity recovery after shear. However, the presence of CM significantly amplified thixotropy and increased suspension viscosity up to 200-fold at higher CNC concentrations (i.e. 4 wt%). Calorimetric measurements revealed the spontaneous character of the CM-CNC interactions (ΔG = -26.7 kJ/mol), with exothermic enthalpy (ΔH = -15.5 kJ/mol) and a positive entropic term (ΔS = 37.38 J/(mol·K)), suggesting a significant hydrophobic contribution to binding affinity. Such interactions increased CM solubility three-fold (25-80 mg mL-1), enabling substantially higher drug loading. At CNC concentrations above 2 wt%, gelation occurred and prevented spray formation. Overall, these results demonstrate that CNCs can function as multifunctional excipients for nasal spray formulations by simultaneously tuning spray performance and enhancing drug solubility.

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Bird Lisa J LJ, Dunn Nicole M NM, Drynan Linda J LJ

A population of Spodoptera litura originating from table grapes in northwest Western Australia in 2024 had 55.1% survival on a discriminating dose of emamectin benzoate in the F1 generation. Survival was stable in this strain (BM6xTG) for the next 7 generations under laboratory selection at the discriminating dose, with 28.9%, 19.6%, and 21.8% mortality in the G4, G6, and G7, respectively. A series of iso-female lines were established from G8 adults and used to generate proxy F2 recombinants (where parental G7 moths were considered as the F0 generation), which were then screened with the discriminating dose of emamectin benzoate. Three lines exhibited 100% survival and were presumed homozygous for resistance. Subsequent quantitative genetic analysis showed that resistance was autosomal, incompletely dominant (DLC = 0.85), and conferred by 1 or a small number of closely linked loci. While there was no major cross-resistance to chlorantraniliprole, indoxacarb, methoxyfenozide, or Vip3A in the BM6xTG strain, it was significantly less sensitive to spinetoram than the laboratory strain. There was a lack of resistance suppression by metabolic inhibitors triphenyl phosphate, diethyl maleate, and piperonyl butoxide, suggesting that metabolic detoxification may not play a role in resistance. A fourth iso-female line was completely insensitive to both emamectin benzoate and chlorantraniliprole, and a complementation test for allelism confirmed multi-resistance to Group 28 and Group 6 insecticides in this strain. The risk that these resistance variants pose to management of S. litura is discussed.

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