Drug Reference for FDA Approved Muscle Relaxants and Related Drugs @ Neurotransmitter.net


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Generic Name:
baclofen

Trade Name:
Lioresal ® [Medtronic]

IUPAC Name:
4-amino-3-(4-chlorophenyl)-butanoic acid


Dosage Forms/Routes:
tablet/oral;
orally disintegrating tablet/oral;
injectable/intrathecal

Major Metabolite:
3-(p-chlorophenyl)-4-hydroxybutyric acid

Database Search Links:
[PubMed]
[Search PubMed for
Randomized Controlled Trials
]

[
PubChem]
[PDSP Ki database]

Initial Approval:
11/22/1977


Manufacturers:

[FDA Search]

Prescribing
Information:

[
Link] (for Kemstro orally disintegrating tablet)

RxList:
[
Link]

Empirical Formula:
C10H12ClNO2

Molecular Mass:
213.661 g/mol

Possible Mechanism of Action:
Baclofen is a GABA-B receptor agonist (1).

Indications:
Baclofen is useful for the alleviation of signs and symptoms of spasticity resulting from multiple sclerosis, particularly for the relief of flexor spasms and concomitant pain, clonus, and muscular rigidity. Patients should have reversible spasticity so that baclofen treatment will aid in restoring residual function.

Baclofen may also be of some value in patients with spinal cord injuries and other spinal cord diseases.

Baclofen is not indicated in the treatment of skeletal muscle spasm resulting from rheumatic disorders.

The efficacy of baclofen in stroke, cerebral palsy, and Parkinson's disease has not been established and therefore, it is not recommended for these conditions.

Chemical Class:
gamma-aminobutyric acid (GABA) analog

PubChem 2D Structure:

"3D" Structure (Requires Chime):
[Link

Generic Name:
carisoprodol

Trade Name:
Soma ® [MedPointe]

IUPAC Name:
[2-(carbamoyloxymethyl)-2-methyl-pentyl] N-
propan-2-ylcarbamate

Dosage Forms/Routes:
tablet/oral

Major Metabolites:
meprobamate;
hydroxycarisprodol;
hydroxymeprobamate

Database Search Links:
[PubMed]
[Search PubMed for
Randomized Controlled Trials
]

[
PubChem]
[PDSP Ki database]

Initial Approval:
04/09/1959


Manufacturers:

[FDA Search]

Prescribing
Information:

[
Link]

RxList:
[
Link]

Empirical Formula:
C12H24N2O4

Molecular Mass:
260.33 g/mol

Possible Mechanism of Action:
Carisoprodol's mechanisms of action are still poorly understood. Carisoprodol's primary metabolite, meprobamate, has barbiturate- like modulatory effects on GABA-A receptors (2). High doses of carisoprodol may induce symptoms that are similar to the symptoms associated with serotonin syndrome (3).

Indications:
Carisoprodol is indicated as an adjunct to rest, physical therapy, and other measures for the relief of discomfort associated with acute, painful musculoskeletal conditions.

Chemical Class:
carbamic acid ester

PubChem 2D Structure:

"3D" Structure (Requires Chime):
[Link

Generic Name:
chlorzoxazone

Trade Name:
Parafon Forte DSC ® [Ortho-McNeil]

IUPAC Name:
5-chloro-3H-benzooxazol-2-one


Dosage Forms/Routes:
tablet/oral;

Major Metabolite:
6-hydroxychlorzoxazone

Database Search Links:
[PubMed]
[Search PubMed for
Randomized Controlled Trials
]

[
PubChem]
[PDSP Ki database]

Initial Approval:
08/15/1958


Manufacturers:

[FDA Search]

Prescribing
Information:

[
Link]

RxList:
[
Link]

Empirical Formula:
C7H4ClNO2

Molecular Mass:
169.565 g/mol

Possible Mechanism of Action:
Chlorzoxazone increases the open probability of IK1 (KCNN4), an intermediate conductance, inwardly-rectifying K+ channel that is calcium-activated (4). The drug does not increase the affinity of the IK1 (SK4) channel for Ca2+ ions, but its effect upon the chanels is Ca2+ dependent (4). In a similar manner, chlorzoxazone also activates SK2 (KCNN2), a small conductance, inwardly-rectifying K+ channel that is calcium-activated (4, 5). Although data related to chlorzoxazone's interaction with SK2 channels is based on experimentation with rat channels (rSK2), the rat protein is 97% identical to the highly homologous human protein, hSK2 (6). Potentially, chlorzoxazone may indirectly affect SK4 and SK2 channels via an interaction with calmodulin or another modulatory molecule (4). The drug may also act indirectly by inducing membrane hyperpolarization and reducing the firing rate in neurons that are involved in muscle spasticity or pain (4). In addition, chlorzoxazone is an inhibitor of inducible nitric oxide synthase (7).

Indications:
Chlorzoxazone is indicated as an adjunct to rest, physical therapy, and other measures for the relief of discomfort associated with acute, painful musculoskeletal conditions.

Chemical Class:
benzoxazole derivative

PubChem 2D Structure:

"3D" Structure (Requires Chime):
[Link

Generic Name:
cyclobenzaprine hydrochloride

Trade Name:
Flexeril ® [Ortho-McNeil]

IUPAC Name:
3-(5H-dibenzo[a,d]cyclohepten-5-ylidene)-
N,N-dimethyl-1-propanamine
hydrochloride

Dosage Forms/Routes:
tablet/oral;
extended release capsule/oral

Major Metabolites:
cyclobenzaprine-10,11-epoxide;
trans-10,11-dihydrodiol-cyclobenzaprine;
cyclobenzaprine N-glucuronid
e

Database Search Links:
[PubMed]
[Search PubMed for
Randomized Controlled Trials
]

[
PubChem]
[PDSP Ki database]

Initial Approval:
08/26/1977


Manufacturers:

[FDA Search]

Prescribing
Information:

[
Link]

RxList:
[
Link]

Empirical Formula:
C20H22ClN

Molecular Mass:
311.848g/mol

Possible Mechanism of Action:
Cyclobenzaprine is an antagonist at one or more of the serotonin 5-HT2 receptor subtypes (8). In neonatal rats, 5-HT2C receptor activation has been associated with a long-lasting amplification of the spinal flexion reflex (9). Thus, cyclobenzaprine is likely to reduce muscle tone via its antagonism of 5-HT2C receptors (8). In addition, the drug exhibits anticholinergic effects (10, 11). Thus, cyclobenzaprine and/or one of its metabolites is likely to be an antagonist at one or more of the muscarinic acetylcholine receptors.

Indications:
Flexeril is indicated as an adjunct to rest and physical therapy for relief of muscle spasm associated with acute, painful musculoskeletal conditions.

Improvement is manifested by relief of muscle spasm and its associated signs and symptoms, namely, pain, tenderness, limitation of motion, and restriction in activities of daily living.

Flexeril should be used only for short periods (up to two or three weeks) because adequate evidence of effectiveness for more prolonged use is not available and because muscle spasm associated with acute, painful musculoskeletal conditions is generally of short duration and specific therapy for longer periods is seldom warranted.

Flexeril has not been found effective in the treatment of spasticity associated with cerebral or spinal cord disease, or in children with cerebral palsy.

Chemical Class:
tricyclic amine salt

PubChem 2D Structure:

"3D" Structure (Requires Chime):
[Link

Generic Name:
diazepam

Trade Name:
Valium ® [
Roche]

IUPAC Name:
9-chloro-2-methyl-6-phenyl-
2,5-diazabicyclo[5.4.0]undeca-
5,8,10,12-tetraen-3-one

Dosage Forms/Routes:
tablet/oral;
injectable/injection;
solution/oral;
concentrate/oral
;
gel/rectal;

Major Metabolites:
nordiazepam;
temazepam;
oxazepam

Database Search Links:
[PubMed]

[Search PubMed for
Randomized Controlled Trials
]

[
PubChem]
[PDSP Ki database]

Initial Approval:
11/15/1963 


Manufacturers:

[FDA Search]

Prescribing Information:
[Link]

RxList:
[Link]

Empirical Formula:
C16H13ClN2O

Molecular Mass:
284.74 g/mol

Possible Mechanism of Action:
Diazepam is a nonselective benzodiazepine agonist (12). Diazepam is also an agonist at peripheral benzodiazepine receptors (13).

Indications:
Diazepam is a useful adjunct for the relief of skeletal muscle spasm due to reflex spasm to local pathology (such as inflammation of the muscles or joints, or secondary to trauma); spasticity caused by upper motor neuron disorders (such as cerebral palsy and paraplegia); athetosis; and stiff-man syndrome. The drug is also indicated as an adjunct treatment for convulsive disorders. In addition, diazepam is indicated for the management of anxiety disorders or for the short-term relief of the symptoms of anxiety. In acute alcohol withdrawal, diazepam may be useful in the symptomatic relief of acute agitation, tremor, impending or acute delirium tremens and hallucinosis.

Chemical Class:
2-keto benzodiazepine

PubChem 2D Structure:

"3D" Structure (Requires Chime):
[
Link] 

Generic Name:
metaxalone

Trade Name:
Skelaxin ® [King Pharmaceuticals]

IUPAC Name:
5-[(3,5-dimethylphenoxy)methyl]-1,3-
oxazolidin-2-one


Dosage Forms/Routes:
tablet/oral

Database Search Links:
[PubMed]
[Search PubMed for
Randomized Controlled Trials
]

[
PubChem]
[PDSP Ki database]

Initial Approval:
08/13/1962


Manufacturers:

[FDA Search]

Prescribing
Information:

[
Link]

RxList:
[
Link]

Empirical Formula:
C12H15NO3

Molecular Mass:
221.252g/mol

Possible Mechanism of Action:
The mechanism of action of metaxalone
in humans has not been established, but may be due to general central nervous system depression (Prescribing Information, 2006). Metaxalone has no direct action on the contractile mechanism of striated muscle, the motor end plate or the nerve fiber (Prescribing Information, 2006).

Indications:
Metaxalone is indicated as an adjunct to rest, physical therapy, and other measures for the relief of discomforts associated with acute, painful musculoskeletal conditions. Metaxalone does not directly relax tense skeletal muscles in humans.

Chemical Class:
oxazolidinone derivative

PubChem 2D Structure:

Generic Name:
methocarbamol

Trade Name:
Robaxin ® [Schwarz]

IUPAC Name:
[2-hydroxy-3-(2-methoxyphenoxy)propyl] carbamate


Dosage Forms/Routes:
tablet/oral;
injectable/injection

Database Search Links:
[PubMed]
[Search PubMed for
Randomized Controlled Trials
]

[
PubChem]
[PDSP Ki database]

Initial Approval:
07/16/1957


Manufacturers:

[FDA Search]

Prescribing
Information:

[
Link] (tablet)
[Link] (injectable)

RxList:
[
Link]

Empirical Formula:
C11H15NO5

Molecular Mass:
241.241g/mol

Possible Mechanism of Action:
The mechanism of action of methocarbamol in humans has not been established, but may be due to general CNS depression (Prescribing Information, 2003). It has no direct action on the contractile mechanism of striated muscle, the motor end plate or the nerve fiber (Prescribing Information, 2003).

Indications:
Methocarbamol is indicated as an adjunct to rest, physical therapy, and other measures for the relief of discomforts associated with acute, painful musculoskeletal conditions. Methocarbamol does not directly relax tense skeletal muscles in humans.

Chemical Class:
carbamic acid ester; derivative of guaifenesin

PubChem 2D Structure:

"3D" Structure (Requires Chime):
[Link

Generic Name:
orphenadrine citrate

Trade Name:
Norflex ® [Graceway]

IUPAC Name:
N,N-dimethyl-2-[(2-methylphenyl)-
phenyl-methoxy]-ethanamine


Dosage Forms/Routes:
injectable/injection;
extended release tablet/oral

Major Metabolites:
N-monodemethylorphenadrine;
N,N-didemethylorphendrine;
orphenadrine N-oxide;
glucuronide/sulfate of
o
-methylbenzhydrylosxyacetic acid;
o-methylbenzhydrol

Database Search Links:
[PubMed]
[Search PubMed for
Randomized Controlled Trials
]

[
PubChem]
[PDSP Ki database]

Initial Approval:
11/04/1959


Manufacturers:

[FDA Search]

Prescribing
Information:

[
Link] (injectable)

RxList:
[
Link]

Empirical Formula:
C24H31NO8

Molecular Mass:
461.505g/mol

Possible Mechanism of Action:
Orphenadrine is a non-competitive antagonist at NMDA receptor complexes (14). In addition, the drug is an antagonist at histamine H1 receptors (15). Orphenadrine may also act as an antagonist at M1, M2, M3, and M4 muscarinic acetylcholine receptors (16).

Indications:
Orphenadrine citrate is indicated as an adjunct to rest, physical therapy, and other measures for the relief of discomfort associated with acute painful musculoskeletal conditions.

Chemical Class:
ethanolamine

PubChem 2D Structure:

"3D" Structure (Requires Chime):
[Link

Generic Name:
tizanidine hydrochloride

Trade Name:
Zanaflex ® [Acorda]

IUPAC Name:
3-chloro-N-(4,5-dihydro-1H-imidazol-2-yl)-8-
thia-7,9-diazabicyclo[4.3.0]non a-2,4,6,9-
tetraen-2-amine hydrochloride


Dosage Forms/Routes:
tablet/oral;
capsule/oral

Major Metabolites:
(5-chloro-4-(2-imidazolin-4-on-2-ylamino)-
2,1,3-benzothiazdiazole;
5-chloro-4-(guanidino)-2,1,3-benzothiazdiazole

Database Search Links:
[PubMed]
[Search PubMed for
Randomized Controlled Trials
]

[
PubChem]
[PDSP Ki database]

Initial Approval:
11/27/1996


Manufacturers:

[FDA Search]

Prescribing
Information:

[
Link]

RxList:
[
Link]

Empirical Formula:
C9H9Cl2N5S

Molecular Mass:
290.173g/mol

Possible Mechanism of Action:
Tizanidine is an agonist at imidazoline receptors (17, 18, 19). It is also an agonist at alpha-2 andrenoceptors (18, 19).

Indications:
Tizanidine is a short-acting drug for the management of spasticity. Because of the short duration of effect, treatment with tizanidine should be reserved for those daily activities and times when relief of spasticity is most important.

Chemical Class:
imidazoline derivative

PubChem 2D Structure:

"3D" Structure (Requires Chime):
[Link

References:

1. Froestl W, Mickel SJ, Hall RG, von Sprecher G, Strub D, Baumann PA, Brugger F, Gentsch C, Jaekel J, Olpe HR
Phosphinic acid analogues of GABA. 1. New potent and selective GABAB agonists.
J Med Chem. 1995 Aug 18;38(17):3297-312. [Abstract]

2. Rho JM, Donevan SD, Rogawski MA
Barbiturate-like actions of the propanediol dicarbamates felbamate and meprobamate.
J Pharmacol Exp Ther. 1997 Mar;280(3):1383-91. [PDF]

3. Bramness JG, Mørland J, Sørlid HK, Rudberg N, Jacobsen D
Carisoprodol intoxications and serotonergic features.
Clin Toxicol (Phila). 2005;43(1):39-45. [Abstract]


4. Syme CA, Gerlach AC, Singh AK, Devor DC
Pharmacological activation of cloned intermediate- and small-conductance Ca(2+)-activated K(+) channels.
Am J Physiol Cell Physiol. 2000 Mar;278(3):C570-81. [Full Text]


5
. Cao Y, Dreixler JC, Roizen JD, Roberts MT, Houamed KM
Modulation of recombinant small-conductance Ca(2+)-activated K(+) channels by the muscle relaxant chlorzoxazone and structurally related compounds.
J Pharmacol Exp Ther. 2001 Mar;296(3):683-9. [Full Text]

6. Desai R, Peretz A, Idelson H, Lazarovici P, Attali B
Ca2+-activated K+ channels in human leukemic Jurkat T cells. Molecular cloning, biochemical and functional characterization.
J Biol Chem. 2000 Dec 22;275(51):39954-63. [Full Text]

7. Grant SK, Green BG, Wang R, Pacholok SG, Kozarich JW
Characterization of inducible nitric-oxide synthase by cytochrome P-450 substrates and inhibitors. Inhibition by chlorzoxazone.
J Biol Chem. 1997 Jan 10;272(2):977-83. [Full Text]

8. Honda M, Nishida T, Ono H
Tricyclic analogs cyclobenzaprine, amitriptyline and cyproheptadine inhibit the spinal reflex transmission through 5-HT(2) receptors.
Eur J Pharmacol. 2003 Jan 1;458(1-2):91-9. [Abstract]

9. Machacek DW, Garraway SM, Shay BL, Hochman S
Serotonin 5-HT(2) receptor activation induces a long-lasting amplification of spinal reflex actions in the rat.
J Physiol. 2001 Nov 15;537(Pt 1):201-7. [Abstract]

10. Brown BR, Womble J
Cyclobenzaprine in intractable pain syndromes with muscle spasm.
JAMA. 1978 Sep 8;240(11):1151-2. [Abstract]

11. Spiller HA, Winter ML, Mann KV, Borys DJ, Muir S, Krenzelok EP
Five-year multicenter retrospective review of cyclobenzaprine toxicity.
J Emerg Med. 1995 Nov-Dec;13(6):781-5. [Abstract]

12. Mihic SJ, Whiting PJ, Klein RL, Wafford KA, Harris RA.
A single amino acid of the human gamma-aminobutyric acid type A receptor gamma 2 subunit determines benzodiazepine efficacy.
J Biol Chem. 1994 Dec 30;269(52):32768-73. [Full Text]

13. Marino F, Cattaneo S, Cosentino M, Rasini E, Di Grazia L, Fietta AM, Lecchini S, Frigo G.
Diazepam stimulates migration and phagocytosis of human neutrophils: possible contribution of peripheral-type benzodiazepine receptors and intracellular calcium.
Pharmacology. 2001 Jul;63(1):42-9. [Abstract]

14. Kornhuber J, Parsons CG, Hartmann S, Retz W, Kamolz S, Thome J, Riederer P
Orphenadrine is an uncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist: binding and patch clamp studies.
J Neural Transm Gen Sect. 1995;102(3):237-46. [Abstract]

15. Rumore MM, Schlichting DA
Analgesic effects of antihistaminics.
Life Sci. 1985 Feb 4;36(5):403-16. [Abstract]

16. Lazareno S, Buckley NJ, Roberts FF
Characterization of muscarinic M4 binding sites in rabbit lung, chicken heart, and NG108-15 cells.
Mol Pharmacol. 1990 Dec;38(6):805-15. [Abstract]

17. Kino Y, Tanabe M, Honda M, Ono H
Involvement of supraspinal imidazoline receptors and descending monoaminergic pathways in tizanidine-induced inhibition of rat spinal reflexes.
J Pharmacol Sci. 2005 Sep;99(1):52-60. [Full Text]

18. Honda M, Sekiguchi Y, Sato N, Ono H
Involvement of imidazoline receptors in the centrally acting muscle-relaxant effects of tizanidine.
Eur J Pharmacol. 2002 Jun 12;445(3):187-93. [Abstract]

19. Muramatsu I, Kigoshi S
Tizanidine may discriminate between imidazoline-receptors and alpha 2-adrenoceptors.
Jpn J Pharmacol. 1992 Aug;59(4):457-9. [Full Text]