Orphenadrine
Encyclopedia
Orphenadrine is an anticholinergic
drug
of the ethanolamine
antihistamine
class with prominent CNS and peripheral actions used to treat painful muscle spasms, other similar conditions, as well as the treatment of some aspects of Parkinson's Disease
. It is closely related to diphenhydramine
. Therefore, it is related to other drugs used for Parkinson's like benztropine
and trihexyphenidyl
, and it is also structurally related to nefopam
, which is a centrally-acting yet non-opioid analgesic. The combination of anticholinergic effects and CNS penetration make orphenadrine useful for pain
of all etiologies, including pain from: radiculopathy
, muscle pain, headaches, and many other types. Some patients report that it feels like orphenadrine and similar drugs help both NSAIDs and opioids find the pain. Orphenadrine has approximately 58% of the anticholinergic potency of atropine at equivalent doses.
Orphenadrine is most often used against pain
and muscle spasm of various etiologies including lumbago, sciatica
, and injury. It is quite useful against allergic symptoms and other histamine-related effects, such as those from hay fever, other allergies, and histamine release from many opioid
analgesics. Where available for prescription compounding, orphenadrine can also be prepared for topical administration and works slightly better than diphenhydramine for this purpose.
The orphenadrine salt used for Parkinsonism is the hydrochloride, whereas the muscle relaxant tablet are the citrate. The manufacturers' descriptions of orphenadrine indicate that the salts are not interchangeable; one reason may be that the citrate can be irritating when injected.
Euphoria
is an effect reported by many patients and orphenadrine has been investigated for use against depression, as first reported in June 1958 in the American Journal of Psychiatry.
Like many first-generation antihistamines and chemically-similar anticholinergics, orphenadrine can also cause excitement and insomnia, particularly in children and the elderly.
Orphenadrine also works on smooth muscle in a manner identical to that of dicyclomine
, brand name Bentyl, and will impact Irritable Bowel Syndrome
in a similar fashion.
in July 1951. Currently, orphenadrine preparations are made in the United States and Canada by Parke-Davis and other companies including 3M
. Known as Disipal, orphenadrine HCl was advertised by the Riker company for Parkinsonism, low back pain, and having a useful anti-depressant effect which helps in treating such conditions -- http://www.decodog.com/inven/MD/md30554.jpg
of diphenhydramine
. Common brand names of diphenhydramine include: Benadryl
, Sominex
, Nytol
, etc.), and thus indicates orphenadrine belongs to the ethanolamine
family of antihistamines. It is produced by reacting dimethylaminoethanol with 2-methylbenzhydryl chloride. The 2-methylbenzhydryl chloride can be formed via a Grignard reaction
. The free base has a molecular weight of 269.38 and an empirical formula of C18H23NO. The molecular weight of orphenadrine hydrochloride is 305.85, and 461.50 for the citrate.
injuries, skeletal muscle tension, rigidity secondary to afflictions such prolapsed discs, and degenerative soft tissue disease especially in the lower back, neck, and joints. It is used to treat other causes of muscle spasms to potentiate the action of opioid analgesics against moderate to severe neuropathic pain
, and it is also used to treat Parkinson's disease
.
Orphenadrine is also a component of various preparations for use against headaches of various types especially tension and histamine headaches. It is also helpful in many cases of fibromyalgia
.
The effect on neuropathic pain
, which is also in many cases generated by cyclobenzaprine
(Flexeril), atropine
, scopolamine
, hyoscyamine
, trazodone
, many first-generation antihistamines, and chemically related drugs like dicyclomine
, a.k.a. dicycloverine, (Bentyl), trihexyphenidyl
(Artane), first-generation tricyclic antidepressants such as amitriptyline
, and other similar drugs, are said by many patients to seem to "help the painkillers find the pain". A direct analgesic effect of orphenadrine comes from relaxing painful muscle spasms as well as central antimuscarinic (atropine-like anticholinergic, see below) action and possibly its local anaesthetic effects.
The adjuvant analgesic effect of orphenadrine is neither antagonised nor directly duplicated by some other drugs used for this purpose, such as baclofen
(Lioresal), clonidine
(Catapres), gabapentin (Neurontin), and others. Therefore, the effects are largely additive if used in combination (same goes for side effects, however). Such medication protocols need close monitoring by a physician especially when other centrally-acting drugs are being used to treat the pain. Cyclobenzaprine
, tricyclic anti-depressants, and antihistamines do have additive side effects. However, there is usually little improvement in the clinically desired effects in that they duplicate and compete with each other in this respect.
Orphenadrine can be used in protocols for treating chronic and/or recurring pain as an alternative to gabapentin
(Neurontin) as an adjuvant analgesic for management of chronic pain with a neuropathic component amongst those who cannot tolerate the side effects of gabapentin. This is also the case for patients for whom duloxetine
(Cymbalta) is contraindicated. Orphenadrine has fewer side effects than many first-generation anti-depressants, cyclobenzaprine
, trazadone, clonidine
, and other drugs used in chronic pain states.
In the United States and Canada, orphenadrine citrate is supplied as 100 mg controlled-release tablets, 100 mg immediate-release tablets, and 60 mg immediate-release tablets. Orphenadrine hydrochloride is supplied as 50 and 60 mg tablets, a 10 mg/ml oral solution, and 30 mg/ml solution for injection.
Orphenadrine is often available mixed with aspirin
, paracetamol
Anarex, ibuprofen
, caffeine
, and/or codeine
in many places. All orphenadrine preparations require a prescription in the United States, but various oral forms are sold over the counter in Canada. Orphenadrine is also available by prescription in many European and Pacific Rim countries (including Australia). In Belgium, Mexico and Canada single-ingredient and combination products are available over the counter. It is also available over the counter in the Philippines and Thailand as Norgesic (35 mg Orphenadrine Citrate/450 mg Paracetamol
) and Norgesic Forte (50 mg Orphenadrine Citrate/650 mg Paracetamol
) from 3M Pharmaceuticals
. Orphenadrine is not available at this time in Japan, Slovenia, Croatia, China, France and Spain.
The dose to be used in therapy for Parkinson's Disease is 60 mg via the oral, intramuscular, or intravenous route. According to patients for both muscle spasm and Parkinson's Disease, the alternative routes for administration via the mouth (sublingual or buccal) or other transmucosal routes do not appear to impart any therapeutic advantage, and this would seem to include the rectal route as well.
. Also, the somewhat cleaner side effect profile than cyclobenzaprine
increases the therapeutic usefulness of the euphorigenic and anxiolytic effects.
is possible but usually less severe than that caused by opioids. Aside from brief rebound stiffness in some patients, orphenadrine does not produce detectable cessation symptoms after therapy is discontinued.
Anticholinergic
An anticholinergic agent is a substance that blocks the neurotransmitter acetylcholine in the central and the peripheral nervous system. An example of an anticholinergic is dicycloverine, and the classic example is atropine....
drug
Drug
A drug, broadly speaking, is any substance that, when absorbed into the body of a living organism, alters normal bodily function. There is no single, precise definition, as there are different meanings in drug control law, government regulations, medicine, and colloquial usage.In pharmacology, a...
of the ethanolamine
Ethanolamine
Ethanolamine, also called 2-aminoethanol or monoethanolamine , is an organic chemical compound that is both a primary amine and a primary alcohol . Like other amines, monoethanolamine acts as a weak base...
antihistamine
Antihistamine
An H1 antagonist is a histamine antagonist of the H1 receptor that serves to reduce or eliminate effects mediated by histamine, an endogenous chemical mediator released during allergic reactions...
class with prominent CNS and peripheral actions used to treat painful muscle spasms, other similar conditions, as well as the treatment of some aspects of Parkinson's Disease
Parkinson's disease
Parkinson's disease is a degenerative disorder of the central nervous system...
. It is closely related to diphenhydramine
Diphenhydramine
Diphenhydramine hydrochloride is a first-generation antihistamine possessing anticholinergic, antitussive, antiemetic, and sedative properties which is mainly used to treat allergies. Like most other first-generation antihistamines, the drug also has a powerful hypnotic effect, and for this reason...
. Therefore, it is related to other drugs used for Parkinson's like benztropine
Benztropine
Benzatropine , also known as benztropine , is an anticholinergic marketed under the trade name Cogentin which is used in the treatment of Parkinson's disease, parkinsonism, akathisia, and dystonia.- Indications :...
and trihexyphenidyl
Trihexyphenidyl
Trihexyphenidyl , also known as benzhexol, is an antiparkinsonian agent of the antimuscarinic class. It has been in clinical usage for decades...
, and it is also structurally related to nefopam
Nefopam
Nefopam is a centrally-acting but non-opioid analgesic drug of the benzoxazocine chemical class which was developed by Riker Laboratories in the 1960s. It is widely used, mainly in European countries, for the relief of moderate to severe pain as an alternative to opioid analgesic drugs...
, which is a centrally-acting yet non-opioid analgesic. The combination of anticholinergic effects and CNS penetration make orphenadrine useful for pain
Pain
Pain is an unpleasant sensation often caused by intense or damaging stimuli such as stubbing a toe, burning a finger, putting iodine on a cut, and bumping the "funny bone."...
of all etiologies, including pain from: radiculopathy
Radiculopathy
Radiculopathy is not a specific condition, but rather a description of a problem in which one or more nerves are affected and do not work properly . The emphasis is on the nerve root...
, muscle pain, headaches, and many other types. Some patients report that it feels like orphenadrine and similar drugs help both NSAIDs and opioids find the pain. Orphenadrine has approximately 58% of the anticholinergic potency of atropine at equivalent doses.
Orphenadrine is most often used against pain
Pain
Pain is an unpleasant sensation often caused by intense or damaging stimuli such as stubbing a toe, burning a finger, putting iodine on a cut, and bumping the "funny bone."...
and muscle spasm of various etiologies including lumbago, sciatica
Sciatica
Sciatica is a set of symptoms including pain that may be caused by general compression or irritation of one of five spinal nerve roots that give rise to each sciatic nerve, or by compression or irritation of the left or right or both sciatic nerves. The pain is felt in the lower back, buttock, or...
, and injury. It is quite useful against allergic symptoms and other histamine-related effects, such as those from hay fever, other allergies, and histamine release from many opioid
Opioid
An opioid is a psychoactive chemical that works by binding to opioid receptors, which are found principally in the central and peripheral nervous system and the gastrointestinal tract...
analgesics. Where available for prescription compounding, orphenadrine can also be prepared for topical administration and works slightly better than diphenhydramine for this purpose.
The orphenadrine salt used for Parkinsonism is the hydrochloride, whereas the muscle relaxant tablet are the citrate. The manufacturers' descriptions of orphenadrine indicate that the salts are not interchangeable; one reason may be that the citrate can be irritating when injected.
Euphoria
Euphoria
Euphoria is an emotional and mental state defined as a sense of great elation and well being.Euphoria may also refer to:* Euphoria , a genus of scarab beetles* Euphoria, a genus name previously used for the longan and other trees...
is an effect reported by many patients and orphenadrine has been investigated for use against depression, as first reported in June 1958 in the American Journal of Psychiatry.
Like many first-generation antihistamines and chemically-similar anticholinergics, orphenadrine can also cause excitement and insomnia, particularly in children and the elderly.
Orphenadrine also works on smooth muscle in a manner identical to that of dicyclomine
Dicyclomine
Dicyclomine, also known as dicycloverine, is an anticholinergic that blocks muscarinic receptors. Dicycloverine was first synthesized in the United States circa 1947.- Clinical uses :...
, brand name Bentyl, and will impact Irritable Bowel Syndrome
Irritable bowel syndrome
Irritable bowel syndrome is a diagnosis of exclusion. It is a functional bowel disorder characterized by chronic abdominal pain, discomfort, bloating, and alteration of bowel habits in the absence of any detectable organic cause. In some cases, the symptoms are relieved by bowel movements...
in a similar fashion.
History
This drug was first synthesised in the late 1940s in Europe and the citrate and hydrochloride were both patented in the United States by Parke-DavisParke-Davis
Parke-Davis is a subsidiary of the pharmaceutical company Pfizer. Although no longer an independent corporation, it was once America's oldest and largest drug maker, and played an important role in medical history.- History :...
in July 1951. Currently, orphenadrine preparations are made in the United States and Canada by Parke-Davis and other companies including 3M
3M
3M Company , formerly known as the Minnesota Mining and Manufacturing Company, is an American multinational conglomerate corporation based in Maplewood, Minnesota, United States....
. Known as Disipal, orphenadrine HCl was advertised by the Riker company for Parkinsonism, low back pain, and having a useful anti-depressant effect which helps in treating such conditions -- http://www.decodog.com/inven/MD/md30554.jpg
Chemistry
Orphenadrine is a methylated derivativeDerivative (chemistry)
In chemistry, a derivative is a compound that is derived from a similar compound by some chemical or physical process. In the past it was also used to mean a compound that can be imagined to arise from another compound, if one atom is replaced with another atom or group of atoms, but modern...
of diphenhydramine
Diphenhydramine
Diphenhydramine hydrochloride is a first-generation antihistamine possessing anticholinergic, antitussive, antiemetic, and sedative properties which is mainly used to treat allergies. Like most other first-generation antihistamines, the drug also has a powerful hypnotic effect, and for this reason...
. Common brand names of diphenhydramine include: Benadryl
Benadryl
Benadryl is a brand name allergy medicine marketed over-the-counter by Johnson & Johnson subsidiary McNeil Consumer Healthcare. Prior to 2007, Benadryl was marketed by Pfizer Consumer Healthcare...
, Sominex
Sominex
Sominex is a trademarked name for two over the counter sleep aids. In the United States diphenhydramine is marketed under this name by GlaxoSmithKline. In the UK Actavis UK markets Promethazine hydrochloride under the Sominex brand....
, Nytol
Nytol
Nytol is a brand of sleeping pill produced by GlaxoSmithKline. The active ingredient is diphenhydramine hydrochloride, a sedative antihistamine.GlaxoSmithKline acquired the product in 2001 with the purchase of Block Drug....
, etc.), and thus indicates orphenadrine belongs to the ethanolamine
Ethanolamine
Ethanolamine, also called 2-aminoethanol or monoethanolamine , is an organic chemical compound that is both a primary amine and a primary alcohol . Like other amines, monoethanolamine acts as a weak base...
family of antihistamines. It is produced by reacting dimethylaminoethanol with 2-methylbenzhydryl chloride. The 2-methylbenzhydryl chloride can be formed via a Grignard reaction
Grignard reaction
The Grignard reaction is an organometallic chemical reaction in which alkyl- or aryl-magnesium halides add to a carbonyl group in an aldehyde or ketone. This reaction is an important tool for the formation of carbon–carbon bonds...
. The free base has a molecular weight of 269.38 and an empirical formula of C18H23NO. The molecular weight of orphenadrine hydrochloride is 305.85, and 461.50 for the citrate.
Pharmacology
Orphenadrine is known to have the following pharmacology:- mACh receptorMuscarinic acetylcholine receptorMuscarinic receptors, or mAChRs, are acetylcholine receptors that form G protein-coupled in the plasma membranes of certain neurons and other cells...
antagonistReceptor antagonistA receptor antagonist is a type of receptor ligand or drug that does not provoke a biological response itself upon binding to a receptor, but blocks or dampens agonist-mediated responses...
(anticholinergicAnticholinergicAn anticholinergic agent is a substance that blocks the neurotransmitter acetylcholine in the central and the peripheral nervous system. An example of an anticholinergic is dicycloverine, and the classic example is atropine....
) - H1 receptorH1 receptorThe H1 receptor is a histamine receptor belonging to the family of Rhodopsin like G-protein-coupled receptors. This receptor, which is activated by the biogenic amine histamine, is expressed throughout the body, to be specific, in smooth muscles, on vascular endothelial cells, in the heart, and in...
antagonistReceptor antagonistA receptor antagonist is a type of receptor ligand or drug that does not provoke a biological response itself upon binding to a receptor, but blocks or dampens agonist-mediated responses...
(antihistamineAntihistamineAn H1 antagonist is a histamine antagonist of the H1 receptor that serves to reduce or eliminate effects mediated by histamine, an endogenous chemical mediator released during allergic reactions...
) - NMDA receptor antagonistNMDA receptor antagonistNMDA receptor antagonists are a class of anesthetics that work to antagonize, or inhibit the action of, the N-methyl d-aspartate receptor . They are used as anesthesia for animals and, less commonly, for humans; the state of anesthesia they induce is referred to as dissociative anesthesia...
- NETNorepinephrine transporterThe norepinephrine transporter , also known as solute carrier family 6 member 2 , is a protein that in humans is encoded by the SLC6A2 gene....
blockerReuptake inhibitorA reuptake inhibitor , also known as a transporter blocker, is a drug that inhibits the plasmalemmal transporter-mediated reuptake of a neurotransmitter from the synapse into the pre-synaptic neuron, leading to an increase in the extracellular concentrations of the neurotransmitter and therefore an...
(norepinephrine reuptake inhibitorNorepinephrine reuptake inhibitorA norepinephrine reuptake inhibitor or adrenergic reuptake inhibitor , is a type of drug which acts as a reuptake inhibitor for the neurotransmitters norepinephrine and epinephrine by blocking the action of the norepinephrine transporter...
) - Nav1.7Nav1.7Nav1.7 is a sodium ion channel that in humans is encoded by the SCN9A gene. It is usually expressed at high levels in two types of neurons, the nociceptive neurons at dorsal root ganglion and trigeminal ganglion, and sympathetic ganglion neurons, which are part of the autonomic nervous system.-...
, Nav1.8, and Nav1.9Nav1.9Sodium channel, voltage-gated, type XI, alpha subunit also known as SCN11A or Nav1.9 is a voltage-gated sodium ion channel protein which in humans is encoded by the SCN11A gene....
sodium channel blockerSodium channel blockerSodium channel blockers are agents that impair conduction of sodium ions through sodium channels.-Extracellular:The following naturally produced substances block sodium channels by binding to and occluding the extracellular pore opening of the channel:... - HERGHERGhERG is a gene that codes for a protein known as Kv11.1 potassium ion channel...
potassium channelPotassium channelIn the field of cell biology, potassium channels are the most widely distributed type of ion channel and are found in virtually all living organisms. They form potassium-selective pores that span cell membranes...
blockerPotassium channel blockerPotassium channel blockers are agents which interfere with conduction through potassium channels.-Arrhythmia:Potassium channel blockers used in the treatment of cardiac arrhythmia are classified as class III antiarrhythmic agents.-Mechanism:...
Uses
Orphenadrine is used to treat muscleMuscle
Muscle is a contractile tissue of animals and is derived from the mesodermal layer of embryonic germ cells. Muscle cells contain contractile filaments that move past each other and change the size of the cell. They are classified as skeletal, cardiac, or smooth muscles. Their function is to...
injuries, skeletal muscle tension, rigidity secondary to afflictions such prolapsed discs, and degenerative soft tissue disease especially in the lower back, neck, and joints. It is used to treat other causes of muscle spasms to potentiate the action of opioid analgesics against moderate to severe neuropathic pain
Pain
Pain is an unpleasant sensation often caused by intense or damaging stimuli such as stubbing a toe, burning a finger, putting iodine on a cut, and bumping the "funny bone."...
, and it is also used to treat Parkinson's disease
Parkinson's disease
Parkinson's disease is a degenerative disorder of the central nervous system...
.
Orphenadrine is also a component of various preparations for use against headaches of various types especially tension and histamine headaches. It is also helpful in many cases of fibromyalgia
Fibromyalgia
Fibromyalgia is a medical disorder characterized by chronic widespread pain and allodynia, a heightened and painful response to pressure. It is an example of a diagnosis of exclusion...
.
The effect on neuropathic pain
Neuropathic pain
Neuropathic pain results from lesions or diseases affecting the somatosensory system. It may be associated with abnormal sensations called dysesthesia, which occur spontaneously and allodynia that occurs in response to external stimuli. Neuropathic pain may have continuous and/or episodic ...
, which is also in many cases generated by cyclobenzaprine
Cyclobenzaprine
Cyclobenzaprine is a muscle relaxant medication used to relieve skeletal muscle spasms and associated pain in acute musculoskeletal conditions. It is the most well-studied drug for this application, and it also has been used off-label for fibromyalgia treatment.- Mechanism of action :The mechanism...
(Flexeril), atropine
Atropine
Atropine is a naturally occurring tropane alkaloid extracted from deadly nightshade , Jimson weed , mandrake and other plants of the family Solanaceae. It is a secondary metabolite of these plants and serves as a drug with a wide variety of effects...
, scopolamine
Scopolamine
Scopolamine, also known as levo-duboisine, and hyoscine, is a tropane alkaloid drug with muscarinic antagonist effects. It is among the secondary metabolites of plants from Solanaceae family of plants, such as henbane, jimson weed and Angel's Trumpets , and corkwood...
, hyoscyamine
Hyoscyamine
Hyoscyamine is a tropane alkaloid. It is a secondary metabolite found in certain plants of the Solanaceae family, including henbane , mandrake , jimsonweed , tomato and deadly nightshade...
, trazodone
Trazodone
Trazodone is an antidepressant of the serotonin antagonist and reuptake inhibitor class. It is a phenylpiperazine compound...
, many first-generation antihistamines, and chemically related drugs like dicyclomine
Dicyclomine
Dicyclomine, also known as dicycloverine, is an anticholinergic that blocks muscarinic receptors. Dicycloverine was first synthesized in the United States circa 1947.- Clinical uses :...
, a.k.a. dicycloverine, (Bentyl), trihexyphenidyl
Trihexyphenidyl
Trihexyphenidyl , also known as benzhexol, is an antiparkinsonian agent of the antimuscarinic class. It has been in clinical usage for decades...
(Artane), first-generation tricyclic antidepressants such as amitriptyline
Amitriptyline
Amitriptyline is a tricyclic antidepressant . It is the most widely used TCA and has at least equal efficacy against depression as the newer class of SSRIs...
, and other similar drugs, are said by many patients to seem to "help the painkillers find the pain". A direct analgesic effect of orphenadrine comes from relaxing painful muscle spasms as well as central antimuscarinic (atropine-like anticholinergic, see below) action and possibly its local anaesthetic effects.
The adjuvant analgesic effect of orphenadrine is neither antagonised nor directly duplicated by some other drugs used for this purpose, such as baclofen
Baclofen
Baclofen is a derivative of gamma-aminobutyric acid . It is primarily used to treat spasticity and is under investigation for the treatment of alcoholism....
(Lioresal), clonidine
Clonidine
Clonidine is a sympatholytic medication used to treat medical conditions, such as high blood pressure, some pain conditions, ADHD and anxiety/panic disorder...
(Catapres), gabapentin (Neurontin), and others. Therefore, the effects are largely additive if used in combination (same goes for side effects, however). Such medication protocols need close monitoring by a physician especially when other centrally-acting drugs are being used to treat the pain. Cyclobenzaprine
Cyclobenzaprine
Cyclobenzaprine is a muscle relaxant medication used to relieve skeletal muscle spasms and associated pain in acute musculoskeletal conditions. It is the most well-studied drug for this application, and it also has been used off-label for fibromyalgia treatment.- Mechanism of action :The mechanism...
, tricyclic anti-depressants, and antihistamines do have additive side effects. However, there is usually little improvement in the clinically desired effects in that they duplicate and compete with each other in this respect.
Orphenadrine can be used in protocols for treating chronic and/or recurring pain as an alternative to gabapentin
Gabapentin
Gabapentin is a pharmaceutical drug, specifically a GABA analogue. It was originally developed for the treatment of epilepsy, and currently is also used to relieve neuropathic pain...
(Neurontin) as an adjuvant analgesic for management of chronic pain with a neuropathic component amongst those who cannot tolerate the side effects of gabapentin. This is also the case for patients for whom duloxetine
Duloxetine
Duloxetine is a serotonin-norepinephrine reuptake inhibitor manufactured and marketed by Eli Lilly. It is effective for major depressive disorder and has been shown to be as effective as venlafaxine for generalized anxiety disorder...
(Cymbalta) is contraindicated. Orphenadrine has fewer side effects than many first-generation anti-depressants, cyclobenzaprine
Cyclobenzaprine
Cyclobenzaprine is a muscle relaxant medication used to relieve skeletal muscle spasms and associated pain in acute musculoskeletal conditions. It is the most well-studied drug for this application, and it also has been used off-label for fibromyalgia treatment.- Mechanism of action :The mechanism...
, trazadone, clonidine
Clonidine
Clonidine is a sympatholytic medication used to treat medical conditions, such as high blood pressure, some pain conditions, ADHD and anxiety/panic disorder...
, and other drugs used in chronic pain states.
Preparations
The citrate salt of orphenadrine is available as Norflex, Banflex, Flexon, and X-Otag, and the hydrochloride salt is available as Disipal and Mephenamin.In the United States and Canada, orphenadrine citrate is supplied as 100 mg controlled-release tablets, 100 mg immediate-release tablets, and 60 mg immediate-release tablets. Orphenadrine hydrochloride is supplied as 50 and 60 mg tablets, a 10 mg/ml oral solution, and 30 mg/ml solution for injection.
Orphenadrine is often available mixed with aspirin
Aspirin
Aspirin , also known as acetylsalicylic acid , is a salicylate drug, often used as an analgesic to relieve minor aches and pains, as an antipyretic to reduce fever, and as an anti-inflammatory medication. It was discovered by Arthur Eichengrun, a chemist with the German company Bayer...
, paracetamol
Paracetamol
Paracetamol INN , or acetaminophen USAN , is a widely used over-the-counter analgesic and antipyretic . It is commonly used for the relief of headaches and other minor aches and pains and is a major ingredient in numerous cold and flu remedies...
Anarex, ibuprofen
Ibuprofen
Ibuprofen is a nonsteroidal anti-inflammatory drug used for relief of symptoms of arthritis, fever, as an analgesic , especially where there is an inflammatory component, and dysmenorrhea....
, caffeine
Caffeine
Caffeine is a bitter, white crystalline xanthine alkaloid that acts as a stimulant drug. Caffeine is found in varying quantities in the seeds, leaves, and fruit of some plants, where it acts as a natural pesticide that paralyzes and kills certain insects feeding on the plants...
, and/or codeine
Codeine
Codeine or 3-methylmorphine is an opiate used for its analgesic, antitussive, and antidiarrheal properties...
in many places. All orphenadrine preparations require a prescription in the United States, but various oral forms are sold over the counter in Canada. Orphenadrine is also available by prescription in many European and Pacific Rim countries (including Australia). In Belgium, Mexico and Canada single-ingredient and combination products are available over the counter. It is also available over the counter in the Philippines and Thailand as Norgesic (35 mg Orphenadrine Citrate/450 mg Paracetamol
Paracetamol
Paracetamol INN , or acetaminophen USAN , is a widely used over-the-counter analgesic and antipyretic . It is commonly used for the relief of headaches and other minor aches and pains and is a major ingredient in numerous cold and flu remedies...
) and Norgesic Forte (50 mg Orphenadrine Citrate/650 mg Paracetamol
Paracetamol
Paracetamol INN , or acetaminophen USAN , is a widely used over-the-counter analgesic and antipyretic . It is commonly used for the relief of headaches and other minor aches and pains and is a major ingredient in numerous cold and flu remedies...
) from 3M Pharmaceuticals
3M
3M Company , formerly known as the Minnesota Mining and Manufacturing Company, is an American multinational conglomerate corporation based in Maplewood, Minnesota, United States....
. Orphenadrine is not available at this time in Japan, Slovenia, Croatia, China, France and Spain.
Dosage and delivery
The muscle-relaxant and analgesic dose of orphenadrine is 100 mg when it is a (theoretical) 12-hour extended release tablet; or 60 to 100 mg every 8 hours in the immediate-release form. When compared with extended release tablets of other drugs, Norflex extended-release tablets more frequently than not require dosing every six or eight hours. It is not clear if the extended-release form of orphenadrine is more effective on a milligram basis than the immediate-release formulations.The dose to be used in therapy for Parkinson's Disease is 60 mg via the oral, intramuscular, or intravenous route. According to patients for both muscle spasm and Parkinson's Disease, the alternative routes for administration via the mouth (sublingual or buccal) or other transmucosal routes do not appear to impart any therapeutic advantage, and this would seem to include the rectal route as well.
Side effects
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, restlessness, insomnia, constipation, urine retention, orthostatic hypotension, and euphoria. The drowsiness and similar side effects tend to resolve within the first three to seven days of therapy. The euphoria is slight to moderate and subjectively different from that of both opioids and carisoprodolCarisoprodol
Carisoprodol is a centrally-acting skeletal muscle relaxant. Carisoprodol is slightly soluble in water and freely soluble in alcohol, chloroform and acetone. The drug's solubility is practically independent of pH. Carisoprodol is manufactured and marketed in the United States by Meda Pharmaceuticals...
. Also, the somewhat cleaner side effect profile than cyclobenzaprine
Cyclobenzaprine
Cyclobenzaprine is a muscle relaxant medication used to relieve skeletal muscle spasms and associated pain in acute musculoskeletal conditions. It is the most well-studied drug for this application, and it also has been used off-label for fibromyalgia treatment.- Mechanism of action :The mechanism...
increases the therapeutic usefulness of the euphorigenic and anxiolytic effects.
Interactions
The cautions and contraindications that apply to other antihistamines in its group apply. Dry mouth should be treated to prevent trouble with teeth. One should avoid driving and operating heavy machinery until such time as the effect is known. ConstipationConstipation
Constipation refers to bowel movements that are infrequent or hard to pass. Constipation is a common cause of painful defecation...
is possible but usually less severe than that caused by opioids. Aside from brief rebound stiffness in some patients, orphenadrine does not produce detectable cessation symptoms after therapy is discontinued.
External links
- PubChem Substance Summary: Orphenadrine National Center for Biotechnology.