Repositioning Candidate Details
| Candidate ID: | R1345 |
| Source ID: | DB11160 |
| Source Type: | approved |
| Compound Type: | small molecule |
| Compound Name: | Phenyltoloxamine |
| Synonyms: | Phenyltoloxamine |
| Molecular Formula: | C17H21NO |
| SMILES: | CN(C)CCOC1=CC=CC=C1CC1=CC=CC=C1 |
| Structure: |
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| DrugBank Description: | Phenyltoloxamine is an antihistamine drug with sedative and analgesic effects. It is a H1 receptor blocker and a member of the ethanolamine class of antihistaminergic drugs. It is available in combination products that also contain other analgesics and antitussives such as acetaminophen. Phenyltoloxamine citrate is the more common salt form that acts as an active ingredient in pharmaceutical products and promotes hay fever relief via reversing the effects of histamine. Phenyltoloxamine acts as an adjuvant analgesic, which augments the analgesic effect of acetaminophen. It also potentiates the effects of other drugs, such as codeine and codeine derivatives. Although phenyltoloxamine's ability to potentiate the effects of analgesics may be explained in part by its chemical nature as a first-generation H1 antihistamine that is capable of crossing the blood-brain barrier and causing tranquilizing effects at CNS histamine receptors, many of the drug's specific pharmacokinetics are not readily available - perhaps also because many early (phenyltoloxamine was involved in studies as early as the 1950s) first-generation antihistamines were not optimally investigated . Nevertheless, phenyltoloxamine is used to a fairly limited extent in contemporary medicine, with only very few products involving it as an active ingredient. |
| CAS Number: | 92-12-6 |
| Molecular Weight: | 255.361 |
| DrugBank Indication: | The primary therapeutic use for which phenyltoloxamine is currently indicated is as an adjuvant therapy in various combination products containing an analgesic(s) (either narcotic or non-narcotic), where it is expected to potentiate the pain relieving, anti-tussive, etc. effect(s) of the analgesic component of the product. In that regard, some of these aforementioned combination products are typically indicated for the temporary relief of minor aches and pains like headache, muscular aches, backaches, minor arthritis pain, common cold, toothaches, menstrual cramps, etc ; or perhaps for the treatment of exhausting or non-productive cough, associated with cold or with upper respiratory allergic condition that does not respond to non-narcotic antitussives . |
| DrugBank Pharmacology: | As a member of the first generation H1 antihistamines, it is known that phenyltoloxamine - like virtually all first generation H1 antihistamines - has a propensity for crossing the blood-brain barrier and acting on H1 histamine receptors there to interfere with neurotransmission . The most common results of this kind of first generation H1 antihistamine CNS neurotransmission interference are adverse effects like drowsiness, sedation, somnolence, and fatigue . Given these effects, under specific circumstances like a patient experiencing a pain or a cough that may be preoccupying all of their waking energy and attention, it is perhaps possible that the sedative and tranquilizing characteristics of phenyltoloxamine may be the factors that contribute to its apparent adjunctive analgesic and antitussive actions . |
| DrugBank MoA: | As a first-generation H1 antihistamine, phenyltoloxamine interferes with the agonist activity of histamine at the H1 receptor and are ostensibly used to attenuate inflammatory processes as a means to treat conditions like allergic rhinitis, allergic conjunctivitis, and urticaria . Reduction of the activity of the NF-kB (nuclear factor kappa-light-chain-enhancer of activated B cells) immune response transcription factor via the phospholipase C and phosphatidylinositol (PIP2) signaling pathways also serves to decrease antigen presentation and the expression of pro-inflammatory cytokines, cell adhesion molecules, and chemotactic factors . Moreover, lowering calcium ion concentration leads to increased mast cell stability which reduces further histamine release . Additionally, first-generation antihistamines like phenyltoloxamine readily cross the blood-brain barrier and cause sedation and other adverse central nervous system (CNS) effects, like nervousness and insomnia . By comparison, second-generation antihistamines are more selective for H1 receptors in the peripheral nervous system and do not cross the blood-brain barrier, resulting in fewer adverse drug effects overall . Furthermore, although some studies propose that phenyltoloxamine may possess some intrinsic antispasmodic and distinct local anesthetic properties , the specific mechanisms of action for these effects have not been formalized. Also, even though the combination of phenyltoloxamine's ability to cross the blood-brain barrier and cause various tranquilizing effects may explain to some extent how it may be able to potentiate analgesic effects , there are also studies that observed no potentiating effects associated with phenyltoloxamine use either . |
| Targets: | Histamine H1 receptor inverse agonist |
| Inclusion Criteria: | Therapeutic strategy associated |
| Strategy ID | Strategy | Synonyms | Related Targets | Related Drugs | |
|---|---|---|---|---|---|
| S05 | Anti-inflammatory | inflammatory | Bile acid; TNF-a inhibitor; Dual PPAR-α and -δ agonists; Toll-Like Receptor; (TLR)-4 antagonist; Caspase inhibitor; ASK-1 inhibitor | Ursodeoxycholic Acid; Pentoxifylline; Elafibranor; JKB-121; Emricasan; Selonsertib; | Details |
| Diseases ID | DO ID | Disease Name | Definition | Class | |
|---|---|---|---|---|---|
| I15 | 1290 | Bone disease | A connective tissue disease that affects the structure or development of bone or causes an impairment of normal bone function. http://en.wikipedia.org/wiki/Bone_disease | disease of anatomical entity/ musculoskeletal system disease/connective tissue disease | Details |