Timolol (BioDeep_00000001971)

 

Secondary id: BioDeep_00000016563

human metabolite blood metabolite Chemicals and Drugs


代谢物信息卡片


1-(tert-butylamino)-3-{[4-(morpholin-4-yl)-1,2,5-thiadiazol-3-yl]oxy}propan-2-ol

化学式: C13H24N4O3S (316.1569)
中文名称: 马来酸噻吗洛尔片-d5, 噻吗洛尔
谱图信息: 最多检出来源 Homo sapiens(COVID-19)(plant) 30.74%

分子结构信息

SMILES: CC(C)(C)NCC(COC1=NSN=C1N2CCOCC2)O
InChI: InChI=1S/C13H24N4O3S/c1-13(2,3)14-8-10(18)9-20-12-11(15-21-16-12)17-4-6-19-7-5-17/h10,14,18H,4-9H2,1-3H3

描述信息

Timolol is only found in individuals that have used or taken this drug. It is a beta-adrenergic antagonist similar in action to propranolol. The levo-isomer is the more active. Timolol has been proposed as an antihypertensive, antiarrhythmic, antiangina, and antiglaucoma agent. It is also used in the treatment of migraine disorders and tremor. [PubChem]Like propranolol and nadolol, timolol competes with adrenergic neurotransmitters such as catecholamines for binding at beta(1)-adrenergic receptors in the heart and vascular smooth muscle and beta(2)-receptors in the bronchial and vascular smooth muscle. Beta(1)-receptor blockade results in a decrease in resting and exercise heart rate and cardiac output, a decrease in both systolic and diastolic blood pressure, and, possibly, a reduction in reflex orthostatic hypotension. Beta(2)-blockade results in an increase in peripheral vascular resistance. The exact mechanism whereby timolol reduces ocular pressure is still not known. The most likely action is by decreasing the secretion of aqueous humor.
C - Cardiovascular system > C07 - Beta blocking agents > C07A - Beta blocking agents > C07AA - Beta blocking agents, non-selective
S - Sensory organs > S01 - Ophthalmologicals > S01E - Antiglaucoma preparations and miotics > S01ED - Beta blocking agents
C78272 - Agent Affecting Nervous System > C29747 - Adrenergic Agent > C72900 - Adrenergic Antagonist
D018377 - Neurotransmitter Agents > D018663 - Adrenergic Agents > D018674 - Adrenergic Antagonists
D002317 - Cardiovascular Agents > D000959 - Antihypertensive Agents
D002317 - Cardiovascular Agents > D000889 - Anti-Arrhythmia Agents

同义名列表

6 个代谢物同义名

1-(tert-butylamino)-3-{[4-(morpholin-4-yl)-1,2,5-thiadiazol-3-yl]oxy}propan-2-ol; S(-)-3-morpholino-4-(3-tert-butylamino-2-hydroxypropoxy)-1,2,5-thiadiazole; Timolol maleate; racemic-Timolol; Timolol; Timolol



数据库引用编号

22 个数据库交叉引用编号

分类词条

相关代谢途径

Reactome(0)

BioCyc(0)

PlantCyc(0)

代谢反应

0 个相关的代谢反应过程信息。

Reactome(0)

BioCyc(0)

WikiPathways(0)

Plant Reactome(0)

INOH(0)

PlantCyc(0)

COVID-19 Disease Map(0)

PathBank(0)

PharmGKB(0)

1 个相关的物种来源信息

在这里通过桑基图来展示出与当前的这个代谢物在我们的BioDeep知识库中具有相关联信息的其他代谢物。在这里进行关联的信息来源主要有:

  • PubMed: 来源于PubMed文献库中的文献信息,我们通过自然语言数据挖掘得到的在同一篇文献中被同时提及的相关代谢物列表,这个列表按照代谢物同时出现的文献数量降序排序,取前10个代谢物作为相关研究中关联性很高的代谢物集合展示在桑基图中。
  • NCBI Taxonomy: 通过文献数据挖掘,得到的代谢物物种来源信息关联。这个关联信息同样按照出现的次数降序排序,取前10个代谢物作为高关联度的代谢物集合展示在桑吉图上。
  • Chemical Taxonomy: 在物质分类上处于同一个分类集合中的其他代谢物
  • Chemical Reaction: 在化学反应过程中,存在为当前代谢物相关联的生化反应过程中的反应底物或者反应产物的关联代谢物信息。

点击图上的相关代谢物的名称,可以跳转到相关代谢物的信息页面。

亚细胞结构定位 关联基因列表
Cytoplasm 8 ACE, ALB, AXIN2, CA1, CYP2D6, EDN1, GFAP, VEGFA
Peripheral membrane protein 2 ACHE, AP1S2
Endosome membrane 1 ADRB2
Endoplasmic reticulum membrane 2 CYP2D6, DRD1
Nucleus 6 ACHE, ADRB2, ALB, AXIN2, DRD1, VEGFA
cytosol 5 ALB, AP1S2, AXIN2, CA1, GFAP
centrosome 2 ALB, AXIN2
Cell membrane 6 ACE, ACHE, ADRB2, ADRB3, DRD1, TNF
Cytoplasmic side 1 AP1S2
Multi-pass membrane protein 4 ADRB2, ADRB3, CACNA1I, DRD1
Synapse 1 ACHE
cell surface 3 ACHE, TNF, VEGFA
glutamatergic synapse 1 DRD1
Golgi apparatus 5 ACHE, ADRB2, ALB, AP1S2, VEGFA
Golgi membrane 2 AP1S2, INS
lysosomal membrane 1 AP1S2
neuromuscular junction 1 ACHE
neuronal cell body 1 TNF
presynaptic membrane 1 DRD1
Lysosome 2 ACE, ADRB2
endosome 2 ACE, ADRB2
plasma membrane 10 ACE, ACHE, ADRB2, ADRB3, AXIN2, CACNA1I, DRD1, EDNRA, REN, TNF
Membrane 7 ACE, ACHE, ADRB2, CACNA1I, CYP2D6, REN, VEGFA
apical plasma membrane 1 ADRB2
extracellular exosome 4 ACE, ALB, CA1, LYZ
endoplasmic reticulum 3 ALB, CYP2D6, VEGFA
extracellular space 10 ACE, ACHE, ALB, EDN1, IL6, INS, LYZ, REN, TNF, VEGFA
perinuclear region of cytoplasm 1 ACHE
adherens junction 1 VEGFA
mitochondrion 1 CYP2D6
protein-containing complex 1 ALB
intracellular membrane-bounded organelle 2 AP1S2, CYP2D6
Microsome membrane 1 CYP2D6
Single-pass type I membrane protein 1 ACE
Secreted 8 ACE, ACHE, ALB, EDN1, IL6, INS, REN, VEGFA
extracellular region 10 ACE, ACHE, ALB, EDN1, IL6, INS, LYZ, REN, TNF, VEGFA
Single-pass membrane protein 1 CYP2D6
astrocyte end-foot 1 GFAP
basal part of cell 1 EDN1
Extracellular side 1 ACHE
anchoring junction 1 ALB
ciliary membrane 1 DRD1
external side of plasma membrane 2 ACE, TNF
Secreted, extracellular space, extracellular matrix 1 VEGFA
dendritic spine 1 DRD1
beta-catenin destruction complex 1 AXIN2
Early endosome 2 ADRB2, AP1S2
Membrane, clathrin-coated pit 1 AP1S2
apical part of cell 1 REN
clathrin-coated pit 1 AP1S2
recycling endosome 1 TNF
Single-pass type II membrane protein 1 TNF
postsynaptic membrane 1 DRD1
Membrane raft 1 TNF
GABA-ergic synapse 1 DRD1
extracellular matrix 1 VEGFA
basement membrane 1 ACHE
Cell projection, dendritic spine 1 DRD1
secretory granule 1 VEGFA
intermediate filament 1 GFAP
receptor complex 2 ADRB2, ADRB3
ciliary basal body 1 ALB
cilium 1 DRD1
cell projection 1 GFAP
phagocytic cup 1 TNF
centriole 1 ALB
brush border membrane 1 ACE
spindle pole 1 ALB
blood microparticle 1 ALB
non-motile cilium 1 DRD1
sperm midpiece 1 ACE
Lipid-anchor, GPI-anchor 1 ACHE
Endomembrane system 1 AP1S2
endosome lumen 1 INS
Cytoplasmic vesicle membrane 1 AP1S2
Cell projection, dendrite 1 DRD1
cell body 1 GFAP
side of membrane 1 ACHE
intermediate filament cytoskeleton 1 GFAP
basal plasma membrane 1 ACE
trans-Golgi network membrane 1 AP1S2
secretory granule lumen 1 INS
Golgi lumen 1 INS
endoplasmic reticulum lumen 3 ALB, IL6, INS
platelet alpha granule lumen 2 ALB, VEGFA
voltage-gated calcium channel complex 1 CACNA1I
specific granule lumen 1 LYZ
tertiary granule lumen 1 LYZ
transport vesicle 2 EDN1, INS
azurophil granule lumen 1 LYZ
Endoplasmic reticulum-Golgi intermediate compartment membrane 1 INS
neuronal dense core vesicle 1 ADRB2
clathrin-coated endocytic vesicle membrane 1 ADRB2
synaptic cleft 1 ACHE
AP-type membrane coat adaptor complex 1 AP1S2
membrane coat 1 AP1S2
AP-1 adaptor complex 1 AP1S2
Cell projection, cilium membrane 1 DRD1
cytoplasmic side of lysosomal membrane 1 GFAP
[Tumor necrosis factor, soluble form]: Secreted 1 TNF
rough endoplasmic reticulum lumen 1 EDN1
Weibel-Palade body 1 EDN1
interleukin-6 receptor complex 1 IL6
[Angiotensin-converting enzyme, soluble form]: Secreted 1 ACE
[Isoform Testis-specific]: Cell membrane 1 ACE
G protein-coupled receptor complex 1 DRD1
[N-VEGF]: Cytoplasm 1 VEGFA
[VEGFA]: Secreted 1 VEGFA
[Isoform L-VEGF189]: Endoplasmic reticulum 1 VEGFA
[Isoform VEGF121]: Secreted 1 VEGFA
[Isoform VEGF165]: Secreted 1 VEGFA
VEGF-A complex 1 VEGFA
[Isoform H]: Cell membrane 1 ACHE
ciliary transition fiber 1 ALB
[C-domain 2]: Secreted 1 TNF
[Tumor necrosis factor, membrane form]: Membrane 1 TNF
[C-domain 1]: Secreted 1 TNF


文献列表

  • Ikhyun Jun, Young Joon Choi, Bo-Rahm Kim, Kyoung Yul Seo, Tae-Im Kim. Activation of ADRB2/PKA Signaling Pathway Facilitates Lipid Synthesis in Meibocytes, and Beta-Blocker Glaucoma Drug Impedes PKA-Induced Lipid Synthesis by Inhibiting ADRB2. International journal of molecular sciences. 2022 Aug; 23(16):. doi: 10.3390/ijms23169478. [PMID: 36012741]
  • Hsin-Ya Yang, Fernando Fierro, Daniel J Yoon, Anthony Gallegos, Stephanie L Osborn, Alan V Nguyen, Thomas R Peavy, William Ferrier, Linda Talken, Betty W Ma, Kristopher G Galang, Andrea Medina Lopez, Daniel R Fregoso, Heather Stewart, Eric A Kurzrock, Athena M Soulika, Jan A Nolta, R Rivkah Isseroff. Combination product of dermal matrix, preconditioned human mesenchymal stem cells and timolol promotes wound healing in the porcine wound model. Journal of biomedical materials research. Part B, Applied biomaterials. 2022 07; 110(7):1615-1623. doi: 10.1002/jbm.b.35022. [PMID: 35099112]
  • Michael Rode, Kolja Nenoff, Kerstin Wirkner, Katrin Horn, Andrej Teren, Ralf Regenthal, Markus Loeffler, Joachim Thiery, Achim Aigner, Janne Pott, Holger Kirsten, Markus Scholz. Impact of medication on blood transcriptome reveals off-target regulations of beta-blockers. PloS one. 2022; 17(4):e0266897. doi: 10.1371/journal.pone.0266897. [PMID: 35446883]
  • Deshan F Sebaratnam, Ana L Rodríguez Bandera, Li-Chuen F Wong, Orli Wargon. Infantile hemangioma. Part 2: Management. Journal of the American Academy of Dermatology. 2021 12; 85(6):1395-1404. doi: 10.1016/j.jaad.2021.08.020. [PMID: 34419523]
  • Li Sun, Chenxia Wang, Yuting Cao, Xinxiang Lv, Limin Tian, Dandan Liu, Lizhong Li, Wenchao Zhao. Fractional 2940-nm Er:YAG laser-assisted drug delivery of timolol maleate for the treatment of deep infantile hemangioma. The Journal of dermatological treatment. 2021 Dec; 32(8):1053-1059. doi: 10.1080/09546634.2020.1729330. [PMID: 32043380]
  • Chenfei Tian, Lu Zeng, Le Tang, Jingni Yu, Mei Ren. Sustained Delivery of Timolol Using Nanostructured Lipid Carriers-Laden Soft Contact Lenses. AAPS PharmSciTech. 2021 Aug; 22(6):212. doi: 10.1208/s12249-021-02096-6. [PMID: 34378099]
  • Ching-Bin Ke, Te-Ling Lu, Jian-Lian Chen. Imprinted β-ketoenamine-linked covalent organic frameworks as dispersive sorbents for the fluorometric determination of timolol. Mikrochimica acta. 2021 02; 188(3):79. doi: 10.1007/s00604-021-04741-0. [PMID: 33569651]
  • Elena Millá Griñó, María Jesús Muniesa Royo, Marta Pazos López. [Therapeutic conflict in patients with COVID-19 and glaucoma]. Medicina clinica. 2020 08; 155(4):182. doi: 10.1016/j.medcli.2020.05.020. [PMID: 32591182]
  • Beth A Drolet, Felix Boakye-Agyeman, Barrie Harper, Kristen Holland, Andrew Lewandowski, Nicole Stefanko, Chiara Melloni. Systemic timolol exposure following topical application to infantile hemangiomas. Journal of the American Academy of Dermatology. 2020 03; 82(3):733-736. doi: 10.1016/j.jaad.2019.02.029. [PMID: 30790601]
  • Luzia Müller, Berit P Jensen, Lucas M Bachmann, Dickson Wong, Anthony P Wells. New technique to reduce systemic side effects of timolol eye drops: The tissue press method-Cross-over clinical trial. Clinical & experimental ophthalmology. 2020 01; 48(1):24-30. doi: 10.1111/ceo.13642. [PMID: 31525271]
  • Tobie D Lee, Olivia W Lee, Kyle R Brimacombe, Lu Chen, Rajarshi Guha, Sabrina Lusvarghi, Bethilehem G Tebase, Carleen Klumpp-Thomas, Robert W Robey, Suresh V Ambudkar, Min Shen, Michael M Gottesman, Matthew D Hall. A High-Throughput Screen of a Library of Therapeutics Identifies Cytotoxic Substrates of P-glycoprotein. Molecular pharmacology. 2019 11; 96(5):629-640. doi: 10.1124/mol.119.115964. [PMID: 31515284]
  • Sang M Lee, Ji-Eun Lee, Sung I Kim, Jae H Jung, Jonghoon Shin. Effect of topical glaucoma medication on tear lipid layer thickness in patients with unilateral glaucoma. Indian journal of ophthalmology. 2019 08; 67(8):1297-1302. doi: 10.4103/ijo.ijo_2100_18. [PMID: 31332113]
  • Ahmed A Khorshed, Mohamed Khairy, Craig E Banks. Electrochemical determination of antihypertensive drugs by employing costless and portable unmodified screen-printed electrodes. Talanta. 2019 Jun; 198(?):447-456. doi: 10.1016/j.talanta.2019.01.117. [PMID: 30876585]
  • Anthony Gallegos, Thomas Peavy, Roy Dixon, Roslyn Rivkah Isseroff. Development of a novel ion-pairing UPLC method with cation-exchange solid-phase extraction for determination of free timolol in human plasma. Journal of chromatography. B, Analytical technologies in the biomedical and life sciences. 2018 Oct; 1096(?):228-235. doi: 10.1016/j.jchromb.2018.08.016. [PMID: 30189376]
  • Navid Niaei, Mohammad Hasanzadeh, Nasrin Shadjou. Molecular interaction of some cardiovascular drugs with human serum albumin at physiological-like conditions: A new approach. Journal of molecular recognition : JMR. 2018 08; 31(8):e2715. doi: 10.1002/jmr.2715. [PMID: 29630759]
  • O O Olawoye, T Ogunleye, T F Sarimiye, T O Bello. Acute angle closure following hemodialysis in a 34-year-old Nigerian female. Nigerian journal of clinical practice. 2018 Jul; 21(7):942-944. doi: 10.4103/njcp.njcp_358_17. [PMID: 29984730]
  • Nadia M Morsi, Ahmed A Aboelwafa, Marwa H S Dawoud. Enhancement of the bioavailability of an antihypertensive drug by transdermal protransfersomal system: formulation and in vivo study. Journal of liposome research. 2018 Jun; 28(2):137-148. doi: 10.1080/08982104.2017.1295989. [PMID: 28264602]
  • Larissa Larsen, Catherine N Tchanque-Fossuo, Farzam Gorouhi, David Boudreault, Chuong Nguyen, Jaime J Fuentes, Robert W Crawford, Sara E Dahle, Thomas Whetzel, R Rivkah Isseroff. Combination therapy of autologous adipose mesenchymal stem cell-enriched, high-density lipoaspirate and topical timolol for healing chronic wounds. Journal of tissue engineering and regenerative medicine. 2018 01; 12(1):186-190. doi: 10.1002/term.2390. [PMID: 27943665]
  • Nupur Shrivastava, Saba Khan, Sanjula Baboota, Javed Ali. Fabrication and Characterization of Timolol Maleate and Brinzolamide Loaded Nanostructured Lipid Carrier System for Ocular Drug Delivery. Current drug delivery. 2018; 15(6):829-839. doi: 10.2174/1566523218666171129205626. [PMID: 29189155]
  • C M Arroyo, D Quinteros, M J Cózar-Bernal, S D Palma, A M Rabasco, M L González-Rodríguez. Ophthalmic administration of a 10-fold-lower dose of conventional nanoliposome formulations caused levels of intraocular pressure similar to those induced by marketed eye drops. European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences. 2018 Jan; 111(?):186-194. doi: 10.1016/j.ejps.2017.09.024. [PMID: 28923571]
  • Carlota Saldanha, Teresa Freitas, Ana Santos Silva-Herdade. Timolol effects on erythrocyte deformability and nitric oxide metabolism. Clinical hemorheology and microcirculation. 2018; 69(1-2):165-173. doi: 10.3233/ch-189110. [PMID: 29630536]
  • Alexandra Robciuc, Joanna Witos, Suvi-Katriina Ruokonen, Antti H Rantamäki, Pierre-Jean Pisella, Susanne K Wiedmer, Juha M Holopainen. Pure Glaucoma Drugs Are Toxic to Immortalized Human Corneal Epithelial Cells, but They Do Not Destabilize Lipid Membranes. Cornea. 2017 Oct; 36(10):1249-1255. doi: 10.1097/ico.0000000000001322. [PMID: 28825921]
  • Taher Alizadeh, Mohammad Reza Ganjali, Faride Rafiei, Maedeh Akhoundian. Synthesis of nano-sized timolol-imprinted polymer via ultrasonication assisted suspension polymerization in silicon oil and its use for the fabrication of timolol voltammetric sensor. Materials science & engineering. C, Materials for biological applications. 2017 Aug; 77(?):300-307. doi: 10.1016/j.msec.2017.03.168. [PMID: 28532033]
  • Yi Zhang, Wendy R Kam, Yang Liu, Xiaomin Chen, David A Sullivan. Influence of Pilocarpine and Timolol on Human Meibomian Gland Epithelial Cells. Cornea. 2017 Jun; 36(6):719-724. doi: 10.1097/ico.0000000000001181. [PMID: 28476050]
  • Jennifer L Dumouchel, Upendra A Argikar, Jaimie Spear, Ann Brown, Christine E Dunne, Valerie M Kramlinger, Amanda L Cirello, Mithat Gunduz. Investigation of Ocular Bioactivation Potential and the Role of Cytochrome P450 2D Enzymes in Rat. Drug metabolism letters. 2017 ; 11(2):102-110. doi: 10.2174/1872312811666170911122919. [PMID: 28891437]
  • Erin Lavik, Markus H Kuehn, Andrew J Shoffstall, Kristyn Atkins, Alina V Dumitrescu, Young H Kwon. Sustained Delivery of Timolol Maleate for Over 90 Days by Subconjunctival Injection. Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics. 2016 12; 32(10):642-649. doi: 10.1089/jop.2016.0042. [PMID: 27835065]
  • Jukka Mäenpää, Olavi Pelkonen. Cardiac safety of ophthalmic timolol. Expert opinion on drug safety. 2016 Nov; 15(11):1549-1561. doi: 10.1080/14740338.2016.1225718. [PMID: 27534869]
  • M L González-Rodríguez, C M Arroyo, M J Cózar-Bernal, P L González-R, J M León, M Calle, D Canca, A M Rabasco. Deformability properties of timolol-loaded transfersomes based on the extrusion mechanism. Statistical optimization of the process. Drug development and industrial pharmacy. 2016 Oct; 42(10):1683-94. doi: 10.3109/03639045.2016.1165691. [PMID: 26981839]
  • Chelvin C A Sng, Maria Cecilia D Aquino, Jiemin Liao, Ce Zheng, Marcus Ang, Paul T K Chew. Anterior segment morphology after acute primary angle closure treatment: a randomised study comparing iridoplasty and medical therapy. The British journal of ophthalmology. 2016 Apr; 100(4):542-8. doi: 10.1136/bjophthalmol-2015-307087. [PMID: 26294102]
  • Kai Kaarniranta, Kirsi Ikäheimo, Eliisa Mannermaa, Auli Ropo. Pharmacokinetics, Efficacy, and Safety of the Preservative-free Fixed Combination of Tafluprost 0.0015\% and Timolol 0.5\% in Healthy Volunteers: A Phase I Comparison vs. the Corresponding Preservative-free Monotherapies. Clinical pharmacokinetics. 2016 Apr; 55(4):485-94. doi: 10.1007/s40262-015-0331-x. [PMID: 26391697]
  • Lisa Weibel, Marjam J Barysch, Helene S Scheer, Ingo Königs, Kathrin Neuhaus, Clemens Schiestl, Katharina Rentsch, Daniel M Müller, Martin Theiler. Topical Timolol for Infantile Hemangiomas: Evidence for Efficacy and Degree of Systemic Absorption. Pediatric dermatology. 2016 Mar; 33(2):184-90. doi: 10.1111/pde.12767. [PMID: 26840644]
  • Fuhong Qin, Li Zeng, Yongtao Zhu, Jingjing Cao, Xiaohui Wang, Wei Liu. Preparation and evaluation of a timolol maleate drug-resin ophthalmic suspension as a sustained-release formulation in vitro and in vivo. Drug development and industrial pharmacy. 2016; 42(4):535-45. doi: 10.3109/03639045.2015.1085872. [PMID: 26368660]
  • Shinichiro Fuma, Masamitsu Shimazawa, Tomoyo Imamura, Yusuke Kanno, Norihito Takano, Kazuhiro Tsuruma, Hideaki Hara. Neuroprotective Effect of Ocular Hypotensive Drugs: Latanoprost/Timolol in Combination Are More Effective than Each as Monotherapy in RGC-5. Biological & pharmaceutical bulletin. 2016; 39(2):192-8. doi: 10.1248/bpb.b15-00584. [PMID: 26830479]
  • Yajing Qiu, Jingyan Yang, Minyan Chen, Lei Chang, Tianyou Wang, Gang Ma, Yunbo Jin, Hui Chen, Xiaoxi Lin. A prospective self-controlled study of topical timolol 0.5\% cream for large superficial infantile hemangiomas. The Journal of dermatology. 2015 Apr; 42(4):363-6. doi: 10.1111/1346-8138.12786. [PMID: 25656976]
  • Carolina Boiero, Daniel Allemandi, Marcela Longhi, Juan M Llabot. RP-HPLC method development for the simultaneous determination of timolol maleate and human serum albumin in albumin nanoparticles. Journal of pharmaceutical and biomedical analysis. 2015; 111(?):186-9. doi: 10.1016/j.jpba.2015.03.031. [PMID: 25890214]
  • Jukka Mäenpää, Marjo Volotinen-Maja, Hannu Kautiainen, Mikko Neuvonen, Mikko Niemi, Pertti J Neuvonen, Janne T Backman. Paroxetine markedly increases plasma concentrations of ophthalmic timolol; CYP2D6 inhibitors may increase the risk of cardiovascular adverse effects of 0.5\% timolol eye drops. Drug metabolism and disposition: the biological fate of chemicals. 2014 Dec; 42(12):2068-76. doi: 10.1124/dmd.114.059576. [PMID: 25261563]
  • Hilal Gokturk, N Nuray Ulusu, Muslum Gok, Erkan Tuncay, Belgin Can, Belma Turan. Long-term treatment with a beta-blocker timolol attenuates renal-damage in diabetic rats via enhancing kidney antioxidant-defense system. Molecular and cellular biochemistry. 2014 Oct; 395(1-2):177-86. doi: 10.1007/s11010-014-2123-2. [PMID: 24947049]
  • Carl V Migliazzo, John C Hagan. Beta blocker eye drops for treatment of acute migraine. Missouri medicine. 2014 Jul; 111(4):283-8. doi: NULL. [PMID: 25211851]
  • Gang Ma, Pinru Wu, Xiaoxi Lin, Hui Chen, Xiaojie Hu, Yunbo Jin, Yajing Qiu. Fractional carbon dioxide laser-assisted drug delivery of topical timolol solution for the treatment of deep infantile hemangioma: a pilot study. Pediatric dermatology. 2014 May; 31(3):286-91. doi: 10.1111/pde.12299. [PMID: 24602019]
  • Daniel J Warner, Hongming Chen, Louis-David Cantin, J Gerry Kenna, Simone Stahl, Clare L Walker, Tobias Noeske. Mitigating the inhibition of human bile salt export pump by drugs: opportunities provided by physicochemical property modulation, in silico modeling, and structural modification. Drug metabolism and disposition: the biological fate of chemicals. 2012 Dec; 40(12):2332-41. doi: 10.1124/dmd.112.047068. [PMID: 22961681]
  • Suguru Nakagawa, Tomohiko Usui, Seiichi Yokoo, Sachiko Omichi, Mikiko Kimakura, Yosai Mori, Kazunori Miyata, Makoto Aihara, Shiro Amano, Makoto Araie. Toxicity evaluation of antiglaucoma drugs using stratified human cultivated corneal epithelial sheets. Investigative ophthalmology & visual science. 2012 Aug; 53(9):5154-60. doi: 10.1167/iovs.12-9685. [PMID: 22695966]
  • Georgi A Georgiev, Norihiko Yokoi, Slavyana Ivanova, Rumen Krastev, Zdravko Lalchev. Surface chemistry study of the interactions of pharmaceutical ingredients with human meibum films. Investigative ophthalmology & visual science. 2012 Jul; 53(8):4605-15. doi: 10.1167/iovs.12-9907. [PMID: 22695955]
  • Jianxiu Du, Jie Quan, Yadi Wang. Chemiluminescence determination of timolol maleate by gold nanoparticles-catalyzed luminol-N-bromosuccinimide system. Talanta. 2012 Feb; 90(?):117-22. doi: 10.1016/j.talanta.2012.01.014. [PMID: 22340125]
  • N Bonnin, H Nezzar, C Dubray, D Renault, C Olmiere, F Chiambaretta. Plasma levels and systemic safety of 0.1\% unpreserved timolol maleate gel, 0.5\% timolol aqueous solution and 0.5\% timolol maleate gel. Journal francais d'ophtalmologie. 2012 Jan; 35(1):9-16. doi: 10.1016/j.jfo.2011.03.012. [PMID: 21992993]
  • Medhat W Shafaa, Neveen M Sabra, Rehab A Fouad. The extended ocular hypotensive effect of positive liposomal cholesterol bound timolol maleate in glaucomatous rabbits. Biopharmaceutics & drug disposition. 2011 Dec; 32(9):507-17. doi: 10.1002/bdd.778. [PMID: 22028305]
  • Fazli Nasir, Zafar Iqbal, Abad Khan, Lateef Ahmad, Yasar Shah, Amir Zada Khan, Jamshaid Ali Khan, Salimullah Khan. Simultaneous determination of timolol maleate, rosuvastatin calcium and diclofenac sodium in pharmaceuticals and physiological fluids using HPLC-UV. Journal of chromatography. B, Analytical technologies in the biomedical and life sciences. 2011 Nov; 879(30):3434-43. doi: 10.1016/j.jchromb.2011.09.021. [PMID: 21963479]
  • E M A F Bastos, R A Santana, A G F Calaça-Costa, P S Thiago. Interaction between Apis mellifera L. and Baccharis dracunculifolia DC, that favours green propolis production in Minas Gerais. Brazilian journal of biology = Revista brasleira de biologia. 2011 Aug; 71(3):727-34. doi: 10.1590/s1519-69842011000400018. [PMID: 21881797]
  • Nazli N Sozmen, Erkan Tuncay, Ayca Bilginoglu, Belma Turan. Profound cardioprotection with timolol in a female rat model of aging-related altered left ventricular function. Canadian journal of physiology and pharmacology. 2011 Apr; 89(4):277-88. doi: 10.1139/y11-018. [PMID: 21526975]
  • Adam K Rudkin, Tim L Gray, Mona Awadalla, Jamie E Craig. Bilateral simultaneous acute angle closure glaucoma precipitated by non-prescription cold and flu medication. Emergency medicine Australasia : EMA. 2010 Oct; 22(5):477-9. doi: 10.1111/j.1742-6723.2010.01338.x. [PMID: 21040488]
  • Xiaofan Sui, Jin Sun, Haiyan Li, Yongjun Wang, Jianfang Liu, Xiaohong Liu, Wenping Zhang, Lijiang Chen, Zhonggui He. Prediction of volume of distribution values in human using immobilized artificial membrane partitioning coefficients, the fraction of compound ionized and plasma protein binding data. European journal of medicinal chemistry. 2009 Nov; 44(11):4455-60. doi: 10.1016/j.ejmech.2009.06.004. [PMID: 19586686]
  • T J van Steeg, V B Boralli, E H J Krekels, P Slijkerman, J Freijer, M Danhof, E C M de Lange. Influence of plasma protein binding on pharmacodynamics: Estimation of in vivo receptor affinities of beta blockers using a new mechanism-based PK-PD modelling approach. Journal of pharmaceutical sciences. 2009 Oct; 98(10):3816-28. doi: 10.1002/jps.21658. [PMID: 19117045]
  • Manthena V S Varma, Bo Feng, R Scott Obach, Matthew D Troutman, Jonathan Chupka, Howard R Miller, Ayman El-Kattan. Physicochemical determinants of human renal clearance. Journal of medicinal chemistry. 2009 Aug; 52(15):4844-52. doi: 10.1021/jm900403j. [PMID: 19445515]
  • A A Attama, S Reichl, C C Müller-Goymann. Sustained release and permeation of timolol from surface-modified solid lipid nanoparticles through bioengineered human cornea. Current eye research. 2009 Aug; 34(8):698-705. doi: 10.1080/02713680903017500. [PMID: 19899997]
  • Hanan M El-Laithy. Novel transdermal delivery of Timolol maleate using sugar esters: preclinical and clinical studies. European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V. 2009 May; 72(1):239-45. doi: 10.1016/j.ejpb.2008.12.003. [PMID: 19126429]
  • Himanshu Gupta, M Aqil, R K Khar, Asgar Ali, Aseem Bhatnagar, Gaurav Mittal, Sanyog Jain. Development and characterization of 99mTc-timolol maleate for evaluating efficacy of in situ ocular drug delivery system. AAPS PharmSciTech. 2009; 10(2):540-6. doi: 10.1208/s12249-009-9238-x. [PMID: 19424806]
  • D Călugăru, M Călugăru. [Bimatoprost therapy in glaucoma]. Oftalmologia (Bucharest, Romania : 1990). 2009; 53(3):34-45. doi: ". [PMID: 19899545]
  • Renu Agarwal, Suresh Kumar Gupta, Sushma Srivastava, Rohit Saxena, S S Agrawal. Intraocular pressure-lowering activity of topical application of Aegle marmelos fruit extract in experimental animal models. Ophthalmic research. 2009; 42(2):112-6. doi: 10.1159/000226216. [PMID: 19556826]
  • Eulogio Besada, Diana Shechtman, Barry J Frauens. Recurrent serous macular detachment after topical ocular hypotensive medication. Clinical & experimental optometry. 2008 Nov; 91(6):551-6. doi: 10.1111/j.1444-0938.2008.00282.x. [PMID: 18537988]
  • Courtney J Collins, Alfonso Berduque, Damien W M Arrigan. Electrochemically modulated liquid-liquid extraction of ionized drugs under physiological conditions. Analytical chemistry. 2008 Nov; 80(21):8102-8. doi: 10.1021/ac800646b. [PMID: 18841995]
  • R Scott Obach, Franco Lombardo, Nigel J Waters. Trend analysis of a database of intravenous pharmacokinetic parameters in humans for 670 drug compounds. Drug metabolism and disposition: the biological fate of chemicals. 2008 Jul; 36(7):1385-405. doi: 10.1124/dmd.108.020479. [PMID: 18426954]
  • Kazuhide Ayajiki, Toshio Kimura, Kohei Yamamizu, Tomio Okamura. Mechanisms underlying mechanical responses to Ephedra herb of isolated rabbit urinary bladder and urethra, a possible stress urinary incontinence therapeutic. Journal of pharmacological sciences. 2008 Jun; 107(2):175-80. doi: 10.1254/jphs.08070fp. [PMID: 18544894]
  • A Izzotti, S C Saccà, B Di Marco, S Penco, A M Bassi. Antioxidant activity of timolol on endothelial cells and its relevance for glaucoma course. Eye (London, England). 2008 Mar; 22(3):445-53. doi: 10.1038/sj.eye.6702737. [PMID: 17293786]
  • Renu Agarwal, Suresh Kumar Gupta, Shyam Sunder Agrawal, Sushma Srivastava, Rohit Saxena. Oculohypotensive effects of foeniculum vulgare in experimental models of glaucoma. Indian journal of physiology and pharmacology. 2008 Jan; 52(1):77-83. doi: ". [PMID: 18831355]
  • Marjo Volotinen, Miia Turpeinen, Ari Tolonen, Jouko Uusitalo, Jukka Mäenpää, Olavi Pelkonen. Timolol metabolism in human liver microsomes is mediated principally by CYP2D6. Drug metabolism and disposition: the biological fate of chemicals. 2007 Jul; 35(7):1135-41. doi: 10.1124/dmd.106.012906. [PMID: 17431033]
  • Eitan Z Rath, Shimon Rumelt. Acute visual loss due to serous retinal detachment from acquired optic pit may be a rare presentation of primary open-angle glaucoma. Canadian journal of ophthalmology. Journal canadien d'ophtalmologie. 2007 Apr; 42(2):339-40. doi: 10.3129/can j ophthalmol.i07-027. [PMID: 17392876]
  • T Nieminen, T Lehtimäki, J Mäenpää, A Ropo, H Uusitalo, M Kähönen. Ophthalmic timolol: plasma concentration and systemic cardiopulmonary effects. Scandinavian journal of clinical and laboratory investigation. 2007; 67(2):237-45. doi: 10.1080/00365510601034736. [PMID: 17366003]
  • Hannu Uusitalo, Mika Kähönen, Auli Ropo, Jukka Mäenpää, Gunilla Bjärnhall, Hans Hedenström, Väinö Turjanmaa. Improved systemic safety and risk-benefit ratio of topical 0.1\% timolol hydrogel compared with 0.5\% timolol aqueous solution in the treatment of glaucoma. Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie. 2006 Nov; 244(11):1491-6. doi: 10.1007/s00417-006-0328-0. [PMID: 16628416]
  • Bernhard T Gehr, Christel Weiss, Franz Porzsolt. The fading of reported effectiveness. A meta-analysis of randomised controlled trials. BMC medical research methodology. 2006 May; 6(?):25. doi: 10.1186/1471-2288-6-25. [PMID: 16689990]
  • U W Laengle, R Markstein, V Schneider, D Roman. Effects of antiglaucoma drugs GLC756, a novel dopamine D2 agonist and D1 antagonist, and timolol on endotoxin-induced TNF-alpha release in serum of rats. European journal of ophthalmology. 2006 May; 16(3):401-6. doi: 10.1177/112067210601600307. [PMID: 16761241]
  • Tuomo Nieminen, Hannu Uusitalo, Jukka Mäenpää, Väinö Turjanmaa, Anders Rane, Stefan Lundgren, Auli Ropo, Riikka Rontu, Terho Lehtimäki, Mika Kähönen. Polymorphisms of genes CYP2D6, ADRB1 and GNAS1 in pharmacokinetics and systemic effects of ophthalmic timolol. A pilot study. European journal of clinical pharmacology. 2005 Dec; 61(11):811-9. doi: 10.1007/s00228-005-0052-4. [PMID: 16315032]
  • Hiroshi Komura, Atsushi Kawase, Masahiro Iwaki. Application of substrate depletion assay for early prediction of nonlinear pharmacokinetics in drug discovery: assessment of nonlinearity of metoprolol, timolol, and propranolol. Journal of pharmaceutical sciences. 2005 Dec; 94(12):2656-66. doi: 10.1002/jps.20490. [PMID: 16258981]
  • Hannu Uusitalo, Juanita Niño, Kari Tahvanainen, Väinö Turjanmaa, Auli Ropo, Juhani Tuominen, Mika Kähönen. Efficacy and systemic side-effects of topical 0.5\% timolol aqueous solution and 0.1\% timolol hydrogel. Acta ophthalmologica Scandinavica. 2005 Dec; 83(6):723-8. doi: 10.1111/j.1600-0420.2005.00562.x. [PMID: 16396651]
  • Stefan Holmstrom, Patricia Buchholz, John Walt, Jannie Wickstrøm, Mark Aagren. Analytic review of bimatoprost, latanoprost and travoprost in primary open angle glaucoma. Current medical research and opinion. 2005 Nov; 21(11):1875-83. doi: 10.1185/030079905x65600. [PMID: 16307709]
  • Tuomo Nieminen, Hannu Uusitalo, Väinö Turjanmaa, Gunilla Bjärnhall, Hans Hedenström, Jukka Mäenpää, Auli Ropo, Pekka Heikkilä, Mika Kähönen. Association between low plasma levels of ophthalmic timolol and haemodynamics in glaucoma patients. European journal of clinical pharmacology. 2005 Jul; 61(5-6):369-74. doi: 10.1007/s00228-005-0945-2. [PMID: 15912390]
  • Yoshiyuki Ohno, Tatuji Iga, Yasuhiko Yamada, Miyuki Nagahara, Makoto Araie, Risa Takayanagi. Pharmacokinetic and pharmacodynamic analysis of systemic effect of topically applied timolol maleate ophthalmic gelling vehicle (Rysmon TG). Current eye research. 2005 Apr; 30(4):319-28. doi: 10.1080/02713680590923294. [PMID: 16020262]
  • Tatsuo Katori, Donald B Hoover, Jeffrey L Ardell, Robert H Helm, Diego F Belardi, Carlo G Tocchetti, Paul R Forfia, David A Kass, Nazareno Paolocci. Calcitonin gene-related peptide in vivo positive inotropy is attributable to regional sympatho-stimulation and is blunted in congestive heart failure. Circulation research. 2005 Feb; 96(2):234-43. doi: 10.1161/01.res.0000152969.42117.ca. [PMID: 15591228]
  • Shay-Whey M Koh, Timothy J Coll, Linda Rose, Yukihiro Matsumoto, Eve J Higginbotham. Antiglaucoma eye drop pulses--increased interleukin-6 secretion by Tenon's capsule fibroblast cultures. Journal of glaucoma. 2004 Jun; 13(3):200-9. doi: 10.1097/00061198-200406000-00005. [PMID: 15118463]
  • Pekka Suomalainen, Christoffer Johans, Tim Söderlund, Paavo K J Kinnunen. Surface activity profiling of drugs applied to the prediction of blood-brain barrier permeability. Journal of medicinal chemistry. 2004 Mar; 47(7):1783-8. doi: 10.1021/jm0309001. [PMID: 15027870]
  • Franco Lombardo, R Scott Obach, Marina Y Shalaeva, Feng Gao. Prediction of human volume of distribution values for neutral and basic drugs. 2. Extended data set and leave-class-out statistics. Journal of medicinal chemistry. 2004 Feb; 47(5):1242-50. doi: 10.1021/jm030408h. [PMID: 14971904]
  • Dimitrios G Fatouros, Joke A Bouwstra. Iontophoretic enhancement of timolol across human dermatomed skin in vitro. Journal of drug targeting. 2004 Jan; 12(1):19-24. doi: 10.1080/10611860410001673591. [PMID: 15203908]
  • Kirsten F Howlett, Matthew J Watt, Mark Hargreaves, Mark A Febbraio. Regulation of glucose kinetics during intense exercise in humans: effects of alpha- and beta-adrenergic blockade. Metabolism: clinical and experimental. 2003 Dec; 52(12):1615-20. doi: 10.1016/s0026-0495(03)00330-5. [PMID: 14669166]
  • Kenji Inoue, Kazuko Okugawa, Satoshi Kato, Yuji Inoue, Goji Tomita, Tetsuro Oshika, Shiro Amano. Ocular factors relevant to anti-glaucomatous eyedrop-related keratoepitheliopathy. Journal of glaucoma. 2003 Dec; 12(6):480-5. doi: 10.1097/00061198-200312000-00007. [PMID: 14646683]
  • Catherine Blondin, Pascale Hamard, Béatrice Cholley, Nicole Haeffner-Cavaillon, Christophe Baudouin. In vitro effects of preserved or preservative-free antiglaucoma medications on human complement system. Current eye research. 2003 Oct; 27(4):253-9. doi: 10.1076/ceyr.27.4.253.16603. [PMID: 14562177]
  • Yoko Goto, Nobuhiro Ibaraki, Kensaku Miyake. Human lens epithelial cell damage and stimulation of their secretion of chemical mediators by benzalkonium chloride rather than latanoprost and timolol. Archives of ophthalmology (Chicago, Ill. : 1960). 2003 Jun; 121(6):835-9. doi: 10.1001/archopht.121.6.835. [PMID: 12796255]
  • J Ostwald, S Graumüller, S Dommerich, M Hoff. [Influence of rhinologic usual and unusual drugs on fibroblasts from nasal polyps in cell culture]. Laryngo- rhino- otologie. 2003 Jun; 82(6):408-15. doi: 10.1055/s-2003-40541. [PMID: 12851848]
  • S M Saw, G Gazzard, K-G Au Eong, D T H Tan. Myopia: attempts to arrest progression. The British journal of ophthalmology. 2002 Nov; 86(11):1306-11. doi: 10.1136/bjo.86.11.1306. [PMID: 12386095]
  • Jean-François Rouland, Patricia Morel-Mandrino, Pierre-Paul Elena, Heinz Polzer, Palaniswamy Sunder Raj. Timolol 0.1\% gel (Nyogel 0.1\% once daily versus conventional timolol 0.5\% solution twice daily: a comparison of efficacy and safety. Ophthalmologica. Journal international d'ophtalmologie. International journal of ophthalmology. Zeitschrift fur Augenheilkunde. 2002 Nov; 216(6):449-54. doi: 10.1159/000067548. [PMID: 12566891]
  • Mayuri B Khamar, Neha Bhatt, Kalpen Patel. Serum lipid profile and timolol gel. Journal of the Indian Medical Association. 2002 Oct; 100(10):620-1. doi: NULL. [PMID: 12452518]
  • J Niño, K Tahvanainen, H Uusitalo, V Turjanmaa, N Hutri-Kähönen, T Kaila, A Ropo, T Kuusela, M Kähönen. Cardiovascular effects of ophthalmic 0.5\% timolol aqueous solution and 0.1\% timolol hydrogel. Clinical physiology and functional imaging. 2002 Jul; 22(4):271-8. doi: 10.1046/j.1475-097x.2002.00430.x. [PMID: 12402450]
  • D F Stamatialis, H H M Rolevink, G H Koops. Controlled transport of timolol maleate through artificial membranes under passive and iontophoretic conditions. Journal of controlled release : official journal of the Controlled Release Society. 2002 Jun; 81(3):335-45. doi: 10.1016/s0168-3659(02)00076-7. [PMID: 12044572]
  • Kenji Kashiwagi, Yoko Iizuka, Shigeo Tsukahara. Neuroprotective effects of nipradilol on purified cultured retinal ganglion cells. Journal of glaucoma. 2002 Jun; 11(3):231-8. doi: 10.1097/00061198-200206000-00012. [PMID: 12140401]
  • Juha-Matti Korte, Timo Kaila, K Matti Saari. Systemic bioavailability and cardiopulmonary effects of 0.5\% timolol eyedrops. Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie. 2002 Jun; 240(6):430-5. doi: 10.1007/s00417-002-0462-2. [PMID: 12107508]
  • Alexander Y Tan, Terry L LeVatte, Michele L Archibald, François Tremblay, Melanie E M Kelly, Balwantray C Chauhan. Timolol concentrations in rat ocular tissues and plasma after topical and intraperitoneal dosing. Journal of glaucoma. 2002 Apr; 11(2):134-42. doi: 10.1097/00061198-200204000-00009. [PMID: 11912361]
  • M I Maguregui, R M Jiménez, R M Alonso, U Akesolo. Quantitative determination of oxprenolol and timolol in urine by capillary zone electrophoresis. Journal of chromatography. A. 2002 Mar; 949(1-2):91-7. doi: 10.1016/s0021-9673(01)01320-6. [PMID: 11999762]
  • Gerjanne J Vianen, Peter P Obels, Guido E E J M van den Thillart, Johan Zaagsma. Beta-adrenoceptors mediate inhibition of lipolysis in adipocytes of tilapia (Oreochromis mossambicus). American journal of physiology. Endocrinology and metabolism. 2002 Feb; 282(2):E318-25. doi: 10.1152/ajpendo.00187.2001. [PMID: 11788363]
  • G Colmenarejo, A Alvarez-Pedraglio, J L Lavandera. Cheminformatic models to predict binding affinities to human serum albumin. Journal of medicinal chemistry. 2001 Dec; 44(25):4370-8. doi: 10.1021/jm010960b. [PMID: 11728183]
  • A H Shedden, J Laurence, A Barrish, T V Olah. Plasma timolol concentrations of timolol maleate: timolol gel-forming solution (TIMOPTIC-XE) once daily versus timolol maleate ophthalmic solution twice daily. Documenta ophthalmologica. Advances in ophthalmology. 2001 Jul; 103(1):73-9. doi: 10.1023/a:1017962731813. [PMID: 11678162]
  • R A Laibovitz, A M VanDenburgh, C Felix, R David, A Batoosingh, A Rosenthal, J Cheetham. Comparison of the ocular hypotensive lipid AGN 192024 with timolol: dosing, efficacy, and safety evaluation of a novel compound for glaucoma management. Archives of ophthalmology (Chicago, Ill. : 1960). 2001 Jul; 119(7):994-1000. doi: 10.1001/archopht.119.7.994. [PMID: 11448321]
  • M Kubo, T Sakuraba, Y Arai, M Nakazawa. [A case of suspected drug-induced ocular pemphigoid]. Nippon Ganka Gakkai zasshi. 2001 Mar; 105(3):189-92. doi: . [PMID: 11280879]