Clinical data | |
---|---|
Trade names | Generic; many brand names [1] |
AHFS/Drugs.com | Monograph |
MedlinePlus | a682162 |
Pregnancy category |
|
Routes of administration | Oral, intravenous, intramuscular |
ATC code | |
Legal status | |
Legal status | |
Pharmacokinetic data | |
Bioavailability | 90% |
Protein binding | 95% |
Metabolism | Hepatic demethylation |
Elimination half-life | 13–20 hours [2] |
Excretion | Renal and biliary |
Identifiers | |
| |
CAS Number | |
PubChem CID | |
IUPHAR/BPS | |
DrugBank | |
ChemSpider | |
UNII | |
KEGG | |
ChEBI | |
ChEMBL | |
CompTox Dashboard (EPA) | |
ECHA InfoCard | 100.001.372 |
Chemical and physical data | |
Formula | C18H23NO |
Molar mass | 269.388 g·mol−1 |
3D model (JSmol) | |
| |
| |
(verify) |
Orphenadrine (sold under many brand names) [1] is an anticholinergic drug of the ethanolamine antihistamine class; it is closely related to diphenhydramine. It is a muscle relaxant that is used to treat muscle pain and to help with motor control in Parkinson's disease, but has largely been superseded by newer drugs.[ citation needed ] It is considered a dirty drug due to its multiple mechanisms of action in different pathways.[ citation needed ] It was discovered and developed in the 1940s.
Orphenadrine is a skeletal muscle relaxant. [1] [3] It is used to relieve pain caused by muscle injuries such as strains and sprains, in combination with rest and physical therapy. [3] A 2004 review found fair evidence that orphenadrine is effective for acute back or neck pain, but found insufficient evidence to establish the relative efficacy of the drug in relation to other drugs in the study. [4]
Orphenadrine and other muscle relaxants are sometimes used to treat pain arising from rheumatoid arthritis but there is no evidence they are effective for that purpose. [5]
In 2003, a Cochrane Review of the use of anticholinergic drugs to improve motor function in Parkinson's disease found that as a class, the drugs are useful for that purpose; it identified one single-site randomised, cross-over study of orphenadrine vs placebo. [6] Although orphenadrine and other anticholinergics have largely been superseded by other drugs; they have a use in alleviating motor function symptoms, and appear to help about 20% of people with Parkinson's. [7]
Orphenadrine has the side effects of the other common antihistamines in large part. Stimulation is somewhat more common than with other related antihistamines, and is especially common in the elderly. Common side effects include dry mouth, dizziness, drowsiness, constipation, urine retention, blurred vision, and headache. [3] Its use in Parkinson's is especially limited by these factors. [6]
Orphenadrine is contraindicated in patients with glaucoma, myasthenia gravis, sphincter relaxation disorders, digestive problems such as peptic ulcers, bowel obstruction, or with enlarged prostate, bladder disorders; that is, they should not consume this drug. [8]
Continuous and/or cumulative use of anticholinergic medications, including first-generation antihistamines, is associated with higher risk of cognitive decline and dementia in older people. [9] [10]
Orphenadrine is known to have these pharmacological properties:
George Rieveschl was a professor of chemistry at the University of Cincinnati and led a research program working on antihistamines. In 1943, one of his students, Fred Huber, synthesized diphenhydramine. Rieveschl worked with Parke-Davis to test the compound, and the company licensed the patent from him. In 1947 Parke-Davis hired him as their Director of Research. While he was there, he led the development of orphenadrine, an analog of diphenhydramine. [21]
Prior to the development of amantadine in the late 1960s and then other drugs, anticholinergics like orphenadrine were the mainstay of Parkinson's treatment. [7]
Orphenadrine has been available as a citrate salt and a hydrochloride salt; in the US as of February 2016 the citrate form was available in tablets, extended release tablets, compounding powder and by injection for acute use in a hospital setting. [1] [22]
Orphenadrine is often available mixed with aspirin, paracetamol/acetaminophen, ibuprofen, caffeine, and/or codeine. [1]
The brand names Norflex and Norgesic are formulations of the citrate salt of orphenadrine and Disipal is the hydrochloride salt. [23]
Orphenadrine is a derivative of diphenhydramine with a methyl group added to one of the phenyl rings. [24]
Orphenadrine has a chiral center and two enantiomers. When employed as a therapeutic agent, it is typically supplied as the racemate. [25]
Enantiomers | |
---|---|
(R)-orphenadrine CAS number: 33425-91-1 | (S)-orphenadrine CAS number: 33425-89-7 |
An analgesic drug, also called simply an analgesic, antalgic, pain reliever, or painkiller, is any member of the group of drugs used for pain management. Analgesics are conceptually distinct from anesthetics, which temporarily reduce, and in some instances eliminate, sensation, although analgesia and anesthesia are neurophysiologically overlapping and thus various drugs have both analgesic and anesthetic effects.
Tricyclic antidepressants (TCAs) are a class of medications that are used primarily as antidepressants. TCAs were discovered in the early 1950s and were marketed later in the decade. They are named after their chemical structure, which contains three rings of atoms. Tetracyclic antidepressants (TeCAs), which contain four rings of atoms, are a closely related group of antidepressant compounds.
A muscle relaxant is a drug that affects skeletal muscle function and decreases the muscle tone. It may be used to alleviate symptoms such as muscle spasms, pain, and hyperreflexia. The term "muscle relaxant" is used to refer to two major therapeutic groups: neuromuscular blockers and spasmolytics. Neuromuscular blockers act by interfering with transmission at the neuromuscular end plate and have no central nervous system (CNS) activity. They are often used during surgical procedures and in intensive care and emergency medicine to cause temporary paralysis. Spasmolytics, also known as "centrally acting" muscle relaxant, are used to alleviate musculoskeletal pain and spasms and to reduce spasticity in a variety of neurological conditions. While both neuromuscular blockers and spasmolytics are often grouped together as muscle relaxant, the term is commonly used to refer to spasmolytics only.
H1 antagonists, also called H1 blockers, are a class of medications that block the action of histamine at the H1 receptor, helping to relieve allergic reactions. Agents where the main therapeutic effect is mediated by negative modulation of histamine receptors are termed antihistamines; other agents may have antihistaminergic action but are not true antihistamines.
Diphenhydramine (DPH) is an antihistamine and sedative mainly used to treat allergies, insomnia, and symptoms of the common cold. It is also less commonly used for tremors in parkinsonism, and nausea. It is taken by mouth, injected into a vein, injected into a muscle, or applied to the skin. Maximal effect is typically around two hours after a dose, and effects can last for up to seven hours.
Anticholinergics are substances that block the action of the acetylcholine (ACh) neurotransmitter at synapses in the central and peripheral nervous system.
Benadryl is a brand of various antihistamine medications used to stop allergies, whose content varies in different countries, but which includes some combination of diphenhydramine, acrivastine, and/or cetirizine.
Chlorphenamine, also known as chlorpheniramine, is an antihistamine used to treat the symptoms of allergic conditions such as allergic rhinitis. It is taken orally. The medication takes effect within two hours and lasts for about 4–6 hours. It is a first-generation antihistamine and works by blocking the H1 receptor.
Cyclobenzaprine, sold under several brand names including, historically, Flexeril, is a muscle relaxer used for muscle spasms from musculoskeletal conditions of sudden onset. It is not useful in cerebral palsy. It is taken by mouth.
Promethazine, sold under the brand name Phenergan among others, is a first-generation antihistamine, sedative, and antiemetic used to treat allergies, insomnia, and nausea. It may also help with some symptoms associated with the common cold and may also be used for sedating people who are agitated or anxious, an effect that has led to some recreational use. Promethazine is taken by mouth (oral), as a rectal suppository, or by injection into a muscle (IM).
Amantadine, sold under the brand name Gocovri among others, is a medication used to treat dyskinesia associated with parkinsonism and influenza caused by type A influenzavirus, though its use for the latter is no longer recommended because of widespread drug resistance. It is also used for a variety of other uses. The drug is taken by mouth.
Doxylamine is an antihistamine medication used to treat insomnia and allergies, and—in combination with pyridoxine (vitamin B6)—to treat morning sickness in pregnant women. It is available over-the-counter and is typically sold under such brand names as Equate, Unisom, or ZzzQuil, among others; and it is used in nighttime cold medicines (e.g., NyQuil) and pain medications containing acetaminophen and/or codeine to help with sleep. The medication is delivered chemically by the salt doxylamine succinate and is taken by mouth. Doxylamine and other first-generation antihistamines are the most widely used sleep medications in the world.Typical side effects of doxylamine (at recommended doses) include dizziness, drowsiness, grogginess, and dry mouth, among others.
Doxepin is a medication belonging to the tricyclic antidepressant (TCA) class of drugs used to treat major depressive disorder, anxiety disorders, chronic hives, and insomnia. For hives it is a less preferred alternative to antihistamines. It has a mild to moderate benefit for sleeping problems. It is used as a cream for itchiness due to atopic dermatitis or lichen simplex chronicus.
Methocarbamol, sold under the brand name Robaxin among others, is a medication used for short-term musculoskeletal pain. It may be used together with rest, physical therapy, and pain medication. It is less preferred in low back pain. It has limited use for rheumatoid arthritis and cerebral palsy. Effects generally begin within half an hour. It is taken by mouth or injection into a vein.
Tripelennamine, sold under the brand name Pyribenzamine by Novartis, is a drug that is used as an antipruritic and first-generation antihistamine. It can be used in the treatment of asthma, hay fever, rhinitis, and urticaria, but is now less common as it has been replaced by newer antihistamines. The drug was patented at CIBA, which merged with Geigy into Ciba-Geigy, and eventually becoming Novartis.
Antihistamines are drugs which treat allergic rhinitis, common cold, influenza, and other allergies. Typically, people take antihistamines as an inexpensive, generic drug that can be bought without a prescription and provides relief from nasal congestion, sneezing, or hives caused by pollen, dust mites, or animal allergy with few side effects. Antihistamines are usually for short-term treatment. Chronic allergies increase the risk of health problems which antihistamines might not treat, including asthma, sinusitis, and lower respiratory tract infection. Consultation of a medical professional is recommended for those who intend to take antihistamines for longer-term use.
Etoxadrol (CL-1848C) is a dissociative anaesthetic drug that has been found to be an NMDA antagonist and produce similar effects to PCP in animals. Etoxadrol, along with another related drug dexoxadrol, were developed as analgesics for use in humans, but development was discontinued in the late 1970s after patients reported side effects such as nightmares and hallucinations.
Nefopam, sold under the brand name Acupan among others, is a centrally acting, non-opioid painkilling medication, with central stimulant and sympathomimetic properties that is primarily used to treat moderate to severe pain.
Arylcyclohexylamines, also known as arylcyclohexamines or arylcyclohexanamines, are a chemical class of pharmaceutical, designer, and experimental drugs.
An analgesic adjuvant is a medication that is typically used for indications other than pain control but provides control of pain (analgesia) in some painful diseases. This is often part of multimodal analgesia, where one of the intentions is to minimize the need for opioids.