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Pharmacology, Pharmacodynamics, Mechanism of action, Pharmacokinetics, Toxicity, Chemical and Physical Properties of Zucapsaicin
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'''Zucapsaicin''' ('''Civanex''') is a [[medication]] used to treat [[osteoarthritis]] of the knee and other [[neuropathic pain]]. It is applied three times daily for a maximum of three months. It reduces pain, and improves articular functions. It is the [[Cis–trans isomerism|''cis''-isomer]] of [[capsaicin]]. '''Civamide''', manufactured by Winston Pharmaceuticals, is produced in formulations for oral, nasal, and topical use (patch and cream).<ref>Winston Pharmaceuticals website {{cite web|url=http://www.winstonlabs.com/productdevelopment/civamide.asp |title=Archived copy |accessdate=November 16, 2011 |deadurl=yes |archiveurl=https://web.archive.org/web/20120425230507/http://www.winstonlabs.com/productdevelopment/civamide.asp |archivedate=April 25, 2012 }}</ref>
'''Zucapsaicin''' ('''Civanex''') is a [[medication]] used to treat [[osteoarthritis]] of the knee and other [[neuropathic pain]]. It is applied three times daily for a maximum of three months. Zucapsaicin is a member of phenols and a member of methoxybenzenes<ref>{{Cite web|url=https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:135952|title=zucapsaicin (CHEBI:135952)|website=www.ebi.ac.uk|access-date=2019-06-25}}</ref> It is a modulator of transient receptor potential cation channel subfamily V member 1 (TRPV-1), also known as the vanilloid or capsaicin receptor 1 that reduces pain, and improves articular functions<ref name=":0">{{Cite web|url=https://www.drugbank.ca/drugs/DB09120|title=Zucapsaicin|website=www.drugbank.ca|access-date=2019-06-25}}</ref><ref name=":1">{{Cite journal|last=Studer|first=Milena|last2=McNaughton|first2=Peter A.|date=2010-10-01|title=Modulation of single-channel properties of TRPV1 by phosphorylation: Modulation of TRPV1 single channels by phosphorylation|url=http://doi.wiley.com/10.1113/jphysiol.2010.190611|journal=The Journal of Physiology|language=en|volume=588|issue=19|pages=3743–3756|doi=10.1113/jphysiol.2010.190611}}</ref>. It is the [[Cis–trans isomerism|''cis''-isomer]] of [[capsaicin]]. '''Civamide''', manufactured by Winston Pharmaceuticals, is produced in formulations for oral, nasal, and topical use (patch and cream).<ref>Winston Pharmaceuticals website {{cite web|url=http://www.winstonlabs.com/productdevelopment/civamide.asp |title=Archived copy |accessdate=November 16, 2011 |deadurl=yes |archiveurl=https://web.archive.org/web/20120425230507/http://www.winstonlabs.com/productdevelopment/civamide.asp |archivedate=April 25, 2012 }}</ref><ref name=":2">{{Cite journal|last=Sałat|first=Kinga|last2=Jakubowska|first2=Anna|last3=Kulig|first3=Katarzyna|date=2014-10|title=Zucapsaicin for the treatment of neuropathic pain|url=http://www.tandfonline.com/doi/full/10.1517/13543784.2014.956079|journal=Expert Opinion on Investigational Drugs|language=en|volume=23|issue=10|pages=1433–1440|doi=10.1517/13543784.2014.956079|issn=1354-3784}}</ref>


Zucapsaicin has been tested for treatment of a variety of conditions associated with ongoing nerve pain. This includes [[herpes simplex]] infections; [[cluster headache]]s and [[migraine]]; and knee [[osteoarthritis]].<ref>Zucapsaicin information from the National Library of Medicine http://druginfo.nlm.nih.gov/drugportal</ref>
Zucapsaicin has been tested for treatment of a variety of conditions associated with ongoing nerve pain. This includes [[herpes simplex]] infections; [[cluster headache]]s and [[migraine]]; and knee [[osteoarthritis]].<ref>Zucapsaicin information from the National Library of Medicine http://druginfo.nlm.nih.gov/drugportal</ref> It was approved by the Health Canada in 2010 as topical cream marketed under the brand name Zuacta but currently not FDA-approved<ref name=":0" />. It has a melting point of 71.5-74.5<ref name=":0" />

== Pharmacology ==
Zucapsaicin mediates an antinociceptive action via acting as an agonist at TRPV1. TRPV1 play an important physiological role of transducing chemical, mechanical and thermal stimuli as well as pain transduction, and participate in pain modulation and perception. They are mainly distributed in C sensory nerve fibers as well as Aẟ fibers to transmit sensory information involving inflammatory and neuropathic pain, and activation of these channels releasesomatostatin, calcitonin gene-related peptide (CGRP) and other neuropeptides (neurokinin A, kassinin), leading to neurogenic inflammation [A19720]. Zucapsaicin is also reported to affect the peptidergic afferent neurons via a desensitization mechanism to decrease the levels of dorsal root ganglia and sciatic calcitonin gene-related peptide (CGRP) and substance P (SP) [L877]<ref name=":0" />
<br />

== Pharmacodynamics ==
Zucapsaicin mediates an antinociceptive action via acting as an agonist at TRPV1. TRPV1 play an important physiological role of transducing chemical, mechanical and thermal stimuli as well as pain transduction, and participate in pain modulation and perception. They are mainly distributed in C sensory nerve fibers as well as Aẟ fibers to transmit sensory information involving inflammatory and neuropathic pain, and activation of these channels releasesomatostatin, calcitonin gene-related peptide (CGRP) and other neuropeptides (neurokinin A, kassinin), leading to neurogenic inflammation <ref name=":2" />. Zucapsaicin is also reported to affect the peptidergic afferent neurons via a desensitization mechanism to decrease the levels of dorsal root ganglia and sciatic calcitonin gene-related peptide (CGRP) and substance P (SP)<ref name=":0" />.
<br />

== Mechanism of action ==
Zucapsaicin excites and desensitizes C-fibers via agonist at TRPV1 on nociceptive neurons. It binds to intracellular sites and initially stimulates the channels, causing burning sensation<ref name=":1" />. The mechanism of pharmacological action of zucapsaicin has not been fully understood yet. It is suggested that this compound, similarly to its trans isomer, is an agonist of the vanilloid receptor VR1 (TRPV1) and a neuronal calcium channel blocker <ref>Bevan SJ, Docherty RJ. Cellular mechanisms of the action of capsaicin. In: Wood J, editor. Capsaicin in the study of pain. Academic Press, London, England; 1993. p. 27-44 </ref><ref>{{Cite journal|last=Anand|first=P.|last2=Bley|first2=K.|date=2011-10|title=Topical capsaicin for pain management: therapeutic potential and mechanisms of action of the new high-concentration capsaicin 8% patch|url=http://dx.doi.org/10.1093/bja/aer260|journal=British Journal of Anaesthesia|volume=107|issue=4|pages=490–502|doi=10.1093/bja/aer260|issn=0007-0912}}</ref>. Capsaicin is able to excite and desensitize C-fibers. As such, it is not only able to cause pain, but also exhibit analgesic properties. Initially, it stimulates TRPV1, which is responsible for a burning sensation. This effect is followed by a longlasting refractory state -- ‘desensitization’ -- during which the previously excited sensory neurons become unresponsive to capsaicin and other stimuli. It was shown that desensitization and tachyphylaxis of TRPV1 channels contribute to capsaicin-induced pain relief<ref>{{Cite journal|last=St. Pierre|first=Michael|last2=Reeh|first2=Peter W.|last3=Zimmermann|first3=Katharina|date=2009-04-30|title=Differential effects of TRPV channel block on polymodal activation of rat cutaneous nociceptors in vitro|url=http://dx.doi.org/10.1007/s00221-009-1808-3|journal=Experimental Brain Research|volume=196|issue=1|pages=31–44|doi=10.1007/s00221-009-1808-3|issn=0014-4819}}</ref> . Desensitization of TRPV1 represents the main mechanism of its inhibitory function.

Three distinct pathways of capsaicin-induced desensitization have been described: i) activation of calcineurin, which results in dephosphorylation of TRPV1; ii) activation of phospholipase C with the subsequent phosphatidylinositol 4,5-biphosphate hydrolysis (rather controversial) and iii) activation of calcium-dependent protein kinase C isoforms and subsequent channel phosphorylation<ref>Stucky CL, Dubin AE, Jeske NA, et al. Roles of transient receptor potential channels in pain. Brain Res Rev 2009;60(1):2-23</ref><ref>{{Citation|title=Transient Receptor Potential Family of Ion Channels|date=2013|url=http://dx.doi.org/10.1007/978-3-642-28753-4_202324|work=Encyclopedia of Pain|pages=4037–4037|publisher=Springer Berlin Heidelberg|isbn=9783642287527|access-date=2019-06-25}}</ref>. Desensitization involves both tachyphylaxis (short-term desensitization) and long-term, persistent, desensitization<ref name=":3">{{Cite journal|last=Szallasi|first=Arpad|last2=Sheta|first2=Mohamed|date=2012-07-11|title=Targeting TRPV1 for pain relief: limits, losers and laurels|url=http://dx.doi.org/10.1517/13543784.2012.704021|journal=Expert Opinion on Investigational Drugs|volume=21|issue=9|pages=1351–1369|doi=10.1517/13543784.2012.704021|issn=1354-3784}}</ref><ref name=":4">{{Cite journal|last=Trevisani|first=Marcello|date=2010-07-26|title=Targeting TRPV1: Challenges and Issues in Pain Management~!2009-12-02~!2010-03-08~!2010-07-26~!|url=http://dx.doi.org/10.2174/1877381801002030037|journal=The Open Drug Discovery Journal|volume=2|issue=3|pages=37–49|doi=10.2174/1877381801002030037|issn=1877-3818}}</ref><ref>{{Cite journal|last=Khairatkar-Joshi|first=Neelima|last2=Szallasi|first2=Arpad|date=2009-01|title=TRPV1 antagonists: the challenges for therapeutic targeting|url=http://dx.doi.org/10.1016/j.molmed.2008.11.004|journal=Trends in Molecular Medicine|volume=15|issue=1|pages=14–22|doi=10.1016/j.molmed.2008.11.004|issn=1471-4914}}</ref>. It is suggested that the downregulation of proalgesic substances (such as SP) and upregulation of analgesic peptides are implicated in desensitization<ref name=":5">Brederson JD, Kym PR, Szallasi A. Targeting TRP channels for pain relief. Eur J Pharmacol 2013;716:61-76 </ref>. The exhaustion of SP reserves renders neurons desensitized and refractory. These mechanisms of desensitization are not fully understood. It is thought that the short-term desensitization is related to capsaicin’s ability to block the intra-axonal transport of NGF, SP and somatostatin<ref>{{Cite journal|last=Papoiu|first=Alexandru DP|last2=Yosipovitch|first2=Gil|date=2010-05-06|title=Topical capsaicin. The fire of a ‘hot’ medicine is reignited|url=http://dx.doi.org/10.1517/14656566.2010.481670|journal=Expert Opinion on Pharmacotherapy|volume=11|issue=8|pages=1359–1371|doi=10.1517/14656566.2010.481670|issn=1465-6566}}</ref>.

The desensitization is a reversible phenomenon. It begins a few hours after capsaicin application and may last even several weeks<ref name=":5" />. The reversible desensitization was found useful in the treatment of pain, whereas the site-specific ablation of sensory nerves transmitting pain stimuli is a promising approach (‘molecular scalpel’) to achieve a permanent pain relief in patients suffering from bone cancer pain or HIV-induced neuropathies<ref name=":3" /><ref name=":4" />. Desensitization and depletion of pronociceptive neurotransmitters induce chemical denervation with a loss of function, which is clinically used in osteoarthritis, diabetic neuropathy, psoriasis and others<ref>{{Cite journal|last=Palazzo|first=Enza|last2=Luongo|first2=Livio|last3=de Novellis|first3=Vito|last4=Berrino|first4=Liberato|last5=Rossi|first5=Francesco|last6=Maione|first6=Sabatino|date=2010-01|title=Moving towards Supraspinal TRPV1 Receptors for Chronic Pain Relief|url=http://dx.doi.org/10.1186/1744-8069-6-66|journal=Molecular Pain|volume=6|pages=1744–8069-6-66|doi=10.1186/1744-8069-6-66|issn=1744-8069}}</ref><ref>{{Cite book|url=http://worldcat.org/oclc/754846779|title=Moving towards supraspinal TRPV1 receptors for chronic pain relief|last=Palazzo, Enza Luongo, Livio de Novellis, Vito Berrino, Liberato Rossi, Francesco Maione, Sabatino|date=2010-10-11|publisher=BioMed Central Ltd|oclc=754846779}}</ref><ref>{{Cite journal|last=Lambert|first=D.G.|date=2009-02|title=Capsaicin receptor antagonists: a promising new addition to the pain clinic|url=http://dx.doi.org/10.1093/bja/aen354|journal=British Journal of Anaesthesia|volume=102|issue=2|pages=153–155|doi=10.1093/bja/aen354|issn=0007-0912}}</ref><ref>{{Cite journal|last=Lambert|first=G. A.|last2=Davis|first2=J. B.|last3=Appleby|first3=J. M.|last4=Chizh|first4=B. A.|last5=Hoskin|first5=K. L.|last6=Zagami|first6=A. S.|date=2009-08-19|title=The effects of the TRPV1 receptor antagonist SB-705498 on trigeminovascular sensitisation and neurotransmission|url=http://dx.doi.org/10.1007/s00210-009-0437-5|journal=Naunyn-Schmiedeberg's Archives of Pharmacology|volume=380|issue=4|pages=311–325|doi=10.1007/s00210-009-0437-5|issn=0028-1298}}</ref>. In dorsal root ganglia and the sciatic nerve, zucapsaicin decreases levels of SP and CGRP, indicating that it influences peptidergic afferent neurons via a desensitization mechanism<ref>{{Cite journal|last=Holzer|first=P.|date=1988-03|title=Local effector functions of capsaicin-sensitive sensory nerve endings: Involvement of tachykinins, calcitonin gene-related peptide and other neuropeptides|url=http://dx.doi.org/10.1016/0306-4522(88)90064-4|journal=Neuroscience|volume=24|issue=3|pages=739–768|doi=10.1016/0306-4522(88)90064-4|issn=0306-4522}}</ref>[41]. When administered topically, the intended targets for zucapsaicin are the neurons that innervate the local area of application. These neurons transmit pain toward the CNS.
<br />

== Pharmacokinetics ==

=== Absorption ===
Zucapsaicin displays low systemic absorption and localizes at the area of application. In animal studies, systemic absorption is 0.075%<ref name=":6">1.    Sanofi Canada: ZUACTA (zucapsaicin cream) product monograph [Link]</ref><ref name=":7">Bernstein JE. Method and compositions of civamide to treat disease of the intestines. WO2011100668 A4; 2011</ref><ref>Schnitzer TJ, Pelletier JP, Haselwood DM. Civamide cream 0.075% in patients with osteoarthritis of the knee: a 12-week randomized controlled clinical trial with a longterm extension. J Rheumatol 2012;39(3):610-20</ref> .

=== Metabolism ===
''In vitro'' studies demonstrates weak to moderate inhibitiory effects on various cytochrome P450 enzymes, although not clinically significant due to low systemic absorption<ref name=":7" />.

=== Route of elimination ===
In rat studies, zucapsaicin and its metabolites are slowly excreted into urine and feces (up to 2/3), with minimal elimination via exhalation following dermal administration<ref name=":6" /><ref name=":7" />.

=== Half life ===
In rats, the elimination half life of zucapsaicin and its metabolites is approximately 7 to 11 hours<ref name=":6" /><ref name=":7" />.
<br />

== Toxicity ==
Most common adverse effects involved application site reactions such as transient burning and warm sensation. Other adverse effects observed in clinical trials are eye irritation, arthralgia, aggravated osteoarthritis, burning sensation, headache, cough and sneezing. Oral LD50 in mouse is >87.5 mg/kg in male and <60 mg/kg in females. Oral LD50 in rats is >90 mg/kg in males and >60 mg/kg in females<ref name=":6" />
<br />

== Chemical and Physical Properties<ref>{{Cite web|url=https://pubchem.ncbi.nlm.nih.gov/|title=|last=|first=|date=|website=|archive-url=|archive-date=|dead-url=|access-date=}}</ref> ==

=== Computed Properties ===
{| class="wikitable"
!Property Name
!Property Value
|-
|Molecular Weight
|305.418 g/mol
|-
|XLogP3-AA
|3.6
|-
|Hydrogen Bond Donor Count
|2
|-
|Hydrogen Bond Acceptor Count
|3
|-
|Rotatable Bond Count
|9
|-
|Exact Mass
|305.199 g/mol
|-
|Monoisotopic Mass
|305.199 g/mol
|-
|Topological Polar Surface Area
|58.6 A^2
|-
|Heavy Atom Count
|22
|-
|Formal Charge
|0
|-
|Complexity
|341
|-
|Isotope Atom Count
|0
|-
|Defined Atom Stereocenter Count
|0
|-
|Undefined Atom Stereocenter Count
|0
|-
|Defined Bond Stereocenter Count
|1
|-
|Undefined Bond Stereocenter Count
|0
|-
|Covalently-Bonded Unit Count
|1
|-
|Compound Is Canonicalized
|Yes
|}


==References==
==References==

Revision as of 13:11, 25 June 2019

Zucapsaicin
Clinical data
Trade namesCivanex
Other namesCivamide; (Z)-Capsaicin; cis-Capsaicin
Routes of
administration		Topical
ATC code
Identifiers
  • (Z)-N-[(4-Hydroxy-3-methoxyphenyl)methyl]-8-methylnon-6-enamide
CAS Number
PubChem CID
ChemSpider
UNII
ECHA InfoCard100.164.527 Edit this at Wikidata
Chemical and physical data
FormulaC18H27NO3
Molar mass305.41188 g/mol g·mol−1
3D model (JSmol)
  • Oc1ccc(cc1OC)CNC(CCCC\C=C/C(C)C)=O
  • InChI=1S/C18H27NO3/c1-14(2)8-6-4-5-7-9-18(21)19-13-15-10-11-16(20)17(12-15)22-3/h6,8,10-12,14,20H,4-5,7,9,13H2,1-3H3,(H,19,21)/b8-6-
  • Key:YKPUWZUDDOIDPM-VURMDHGXSA-N

Zucapsaicin (Civanex) is a medication used to treat osteoarthritis of the knee and other neuropathic pain. It is applied three times daily for a maximum of three months. Zucapsaicin is a member of phenols and a member of methoxybenzenes[1] It is a modulator of transient receptor potential cation channel subfamily V member 1 (TRPV-1), also known as the vanilloid or capsaicin receptor 1 that reduces pain, and improves articular functions[2][3]. It is the cis-isomer of capsaicin. Civamide, manufactured by Winston Pharmaceuticals, is produced in formulations for oral, nasal, and topical use (patch and cream).[4][5]

Zucapsaicin has been tested for treatment of a variety of conditions associated with ongoing nerve pain. This includes herpes simplex infections; cluster headaches and migraine; and knee osteoarthritis.[6] It was approved by the Health Canada in 2010 as topical cream marketed under the brand name Zuacta but currently not FDA-approved[2]. It has a melting point of 71.5-74.5[2]

Pharmacology

Zucapsaicin mediates an antinociceptive action via acting as an agonist at TRPV1. TRPV1 play an important physiological role of transducing chemical, mechanical and thermal stimuli as well as pain transduction, and participate in pain modulation and perception. They are mainly distributed in C sensory nerve fibers as well as Aẟ fibers to transmit sensory information involving inflammatory and neuropathic pain, and activation of these channels releasesomatostatin, calcitonin gene-related peptide (CGRP) and other neuropeptides (neurokinin A, kassinin), leading to neurogenic inflammation [A19720]. Zucapsaicin is also reported to affect the peptidergic afferent neurons via a desensitization mechanism to decrease the levels of dorsal root ganglia and sciatic calcitonin gene-related peptide (CGRP) and substance P (SP) [L877][2]

Pharmacodynamics

Zucapsaicin mediates an antinociceptive action via acting as an agonist at TRPV1. TRPV1 play an important physiological role of transducing chemical, mechanical and thermal stimuli as well as pain transduction, and participate in pain modulation and perception. They are mainly distributed in C sensory nerve fibers as well as Aẟ fibers to transmit sensory information involving inflammatory and neuropathic pain, and activation of these channels releasesomatostatin, calcitonin gene-related peptide (CGRP) and other neuropeptides (neurokinin A, kassinin), leading to neurogenic inflammation [5]. Zucapsaicin is also reported to affect the peptidergic afferent neurons via a desensitization mechanism to decrease the levels of dorsal root ganglia and sciatic calcitonin gene-related peptide (CGRP) and substance P (SP)[2].

Mechanism of action

Zucapsaicin excites and desensitizes C-fibers via agonist at TRPV1 on nociceptive neurons. It binds to intracellular sites and initially stimulates the channels, causing burning sensation[3]. The mechanism of pharmacological action of zucapsaicin has not been fully understood yet. It is suggested that this compound, similarly to its trans isomer, is an agonist of the vanilloid receptor VR1 (TRPV1) and a neuronal calcium channel blocker [7][8]. Capsaicin is able to excite and desensitize C-fibers. As such, it is not only able to cause pain, but also exhibit analgesic properties. Initially, it stimulates TRPV1, which is responsible for a burning sensation. This effect is followed by a longlasting refractory state -- ‘desensitization’ -- during which the previously excited sensory neurons become unresponsive to capsaicin and other stimuli. It was shown that desensitization and tachyphylaxis of TRPV1 channels contribute to capsaicin-induced pain relief[9] . Desensitization of TRPV1 represents the main mechanism of its inhibitory function.

Three distinct pathways of capsaicin-induced desensitization have been described: i) activation of calcineurin, which results in dephosphorylation of TRPV1; ii) activation of phospholipase C with the subsequent phosphatidylinositol 4,5-biphosphate hydrolysis (rather controversial) and iii) activation of calcium-dependent protein kinase C isoforms and subsequent channel phosphorylation[10][11]. Desensitization involves both tachyphylaxis (short-term desensitization) and long-term, persistent, desensitization[12][13][14]. It is suggested that the downregulation of proalgesic substances (such as SP) and upregulation of analgesic peptides are implicated in desensitization[15]. The exhaustion of SP reserves renders neurons desensitized and refractory. These mechanisms of desensitization are not fully understood. It is thought that the short-term desensitization is related to capsaicin’s ability to block the intra-axonal transport of NGF, SP and somatostatin[16].

The desensitization is a reversible phenomenon. It begins a few hours after capsaicin application and may last even several weeks[15]. The reversible desensitization was found useful in the treatment of pain, whereas the site-specific ablation of sensory nerves transmitting pain stimuli is a promising approach (‘molecular scalpel’) to achieve a permanent pain relief in patients suffering from bone cancer pain or HIV-induced neuropathies[12][13]. Desensitization and depletion of pronociceptive neurotransmitters induce chemical denervation with a loss of function, which is clinically used in osteoarthritis, diabetic neuropathy, psoriasis and others[17][18][19][20]. In dorsal root ganglia and the sciatic nerve, zucapsaicin decreases levels of SP and CGRP, indicating that it influences peptidergic afferent neurons via a desensitization mechanism[21][41]. When administered topically, the intended targets for zucapsaicin are the neurons that innervate the local area of application. These neurons transmit pain toward the CNS.

Pharmacokinetics

Absorption

Zucapsaicin displays low systemic absorption and localizes at the area of application. In animal studies, systemic absorption is 0.075%[22][23][24] .

Metabolism

In vitro studies demonstrates weak to moderate inhibitiory effects on various cytochrome P450 enzymes, although not clinically significant due to low systemic absorption[23].

Route of elimination

In rat studies, zucapsaicin and its metabolites are slowly excreted into urine and feces (up to 2/3), with minimal elimination via exhalation following dermal administration[22][23].

Half life

In rats, the elimination half life of zucapsaicin and its metabolites is approximately 7 to 11 hours[22][23].

Toxicity

Most common adverse effects involved application site reactions such as transient burning and warm sensation. Other adverse effects observed in clinical trials are eye irritation, arthralgia, aggravated osteoarthritis, burning sensation, headache, cough and sneezing. Oral LD50 in mouse is >87.5 mg/kg in male and <60 mg/kg in females. Oral LD50 in rats is >90 mg/kg in males and >60 mg/kg in females[22]

Chemical and Physical Properties[25]

Computed Properties

Property Name Property Value
Molecular Weight 305.418 g/mol
XLogP3-AA 3.6
Hydrogen Bond Donor Count 2
Hydrogen Bond Acceptor Count 3
Rotatable Bond Count 9
Exact Mass 305.199 g/mol
Monoisotopic Mass 305.199 g/mol
Topological Polar Surface Area 58.6 A^2
Heavy Atom Count 22
Formal Charge 0
Complexity 341
Isotope Atom Count 0
Defined Atom Stereocenter Count 0
Undefined Atom Stereocenter Count 0
Defined Bond Stereocenter Count 1
Undefined Bond Stereocenter Count 0
Covalently-Bonded Unit Count 1
Compound Is Canonicalized Yes

References

  1. ^ "zucapsaicin (CHEBI:135952)". www.ebi.ac.uk. Retrieved 2019-06-25.
  2. ^ a b c d e "Zucapsaicin". www.drugbank.ca. Retrieved 2019-06-25.
  3. ^ a b Studer, Milena; McNaughton, Peter A. (2010-10-01). "Modulation of single-channel properties of TRPV1 by phosphorylation: Modulation of TRPV1 single channels by phosphorylation". The Journal of Physiology. 588 (19): 3743–3756. doi:10.1113/jphysiol.2010.190611.
  4. ^ Winston Pharmaceuticals website "Archived copy". Archived from the original on April 25, 2012. Retrieved November 16, 2011. {{cite web}}: Unknown parameter |deadurl= ignored (|url-status= suggested) (help)CS1 maint: archived copy as title (link)
  5. ^ a b Sałat, Kinga; Jakubowska, Anna; Kulig, Katarzyna (2014-10). "Zucapsaicin for the treatment of neuropathic pain". Expert Opinion on Investigational Drugs. 23 (10): 1433–1440. doi:10.1517/13543784.2014.956079. ISSN 1354-3784. {{cite journal}}: Check date values in: |date= (help)
  6. ^ Zucapsaicin information from the National Library of Medicine http://druginfo.nlm.nih.gov/drugportal
  7. ^ Bevan SJ, Docherty RJ. Cellular mechanisms of the action of capsaicin. In: Wood J, editor. Capsaicin in the study of pain. Academic Press, London, England; 1993. p. 27-44
  8. ^ Anand, P.; Bley, K. (2011-10). "Topical capsaicin for pain management: therapeutic potential and mechanisms of action of the new high-concentration capsaicin 8% patch". British Journal of Anaesthesia. 107 (4): 490–502. doi:10.1093/bja/aer260. ISSN 0007-0912. {{cite journal}}: Check date values in: |date= (help)
  9. ^ St. Pierre, Michael; Reeh, Peter W.; Zimmermann, Katharina (2009-04-30). "Differential effects of TRPV channel block on polymodal activation of rat cutaneous nociceptors in vitro". Experimental Brain Research. 196 (1): 31–44. doi:10.1007/s00221-009-1808-3. ISSN 0014-4819.
  10. ^ Stucky CL, Dubin AE, Jeske NA, et al. Roles of transient receptor potential channels in pain. Brain Res Rev 2009;60(1):2-23
  11. ^ "Transient Receptor Potential Family of Ion Channels", Encyclopedia of Pain, Springer Berlin Heidelberg, pp. 4037–4037, 2013, ISBN 9783642287527, retrieved 2019-06-25
  12. ^ a b Szallasi, Arpad; Sheta, Mohamed (2012-07-11). "Targeting TRPV1 for pain relief: limits, losers and laurels". Expert Opinion on Investigational Drugs. 21 (9): 1351–1369. doi:10.1517/13543784.2012.704021. ISSN 1354-3784.
  13. ^ a b Trevisani, Marcello (2010-07-26). "Targeting TRPV1: Challenges and Issues in Pain Management~!2009-12-02~!2010-03-08~!2010-07-26~!". The Open Drug Discovery Journal. 2 (3): 37–49. doi:10.2174/1877381801002030037. ISSN 1877-3818.
  14. ^ Khairatkar-Joshi, Neelima; Szallasi, Arpad (2009-01). "TRPV1 antagonists: the challenges for therapeutic targeting". Trends in Molecular Medicine. 15 (1): 14–22. doi:10.1016/j.molmed.2008.11.004. ISSN 1471-4914. {{cite journal}}: Check date values in: |date= (help)
  15. ^ a b Brederson JD, Kym PR, Szallasi A. Targeting TRP channels for pain relief. Eur J Pharmacol 2013;716:61-76
  16. ^ Papoiu, Alexandru DP; Yosipovitch, Gil (2010-05-06). "Topical capsaicin. The fire of a 'hot' medicine is reignited". Expert Opinion on Pharmacotherapy. 11 (8): 1359–1371. doi:10.1517/14656566.2010.481670. ISSN 1465-6566.
  17. ^ Palazzo, Enza; Luongo, Livio; de Novellis, Vito; Berrino, Liberato; Rossi, Francesco; Maione, Sabatino (2010-01). "Moving towards Supraspinal TRPV1 Receptors for Chronic Pain Relief". Molecular Pain. 6: 1744–8069-6-66. doi:10.1186/1744-8069-6-66. ISSN 1744-8069. {{cite journal}}: Check date values in: |date= (help)CS1 maint: unflagged free DOI (link)
  18. ^ Palazzo, Enza Luongo, Livio de Novellis, Vito Berrino, Liberato Rossi, Francesco Maione, Sabatino (2010-10-11). Moving towards supraspinal TRPV1 receptors for chronic pain relief. BioMed Central Ltd. OCLC 754846779.{{cite book}}: CS1 maint: multiple names: authors list (link)
  19. ^ Lambert, D.G. (2009-02). "Capsaicin receptor antagonists: a promising new addition to the pain clinic". British Journal of Anaesthesia. 102 (2): 153–155. doi:10.1093/bja/aen354. ISSN 0007-0912. {{cite journal}}: Check date values in: |date= (help)
  20. ^ Lambert, G. A.; Davis, J. B.; Appleby, J. M.; Chizh, B. A.; Hoskin, K. L.; Zagami, A. S. (2009-08-19). "The effects of the TRPV1 receptor antagonist SB-705498 on trigeminovascular sensitisation and neurotransmission". Naunyn-Schmiedeberg's Archives of Pharmacology. 380 (4): 311–325. doi:10.1007/s00210-009-0437-5. ISSN 0028-1298.
  21. ^ Holzer, P. (1988-03). "Local effector functions of capsaicin-sensitive sensory nerve endings: Involvement of tachykinins, calcitonin gene-related peptide and other neuropeptides". Neuroscience. 24 (3): 739–768. doi:10.1016/0306-4522(88)90064-4. ISSN 0306-4522. {{cite journal}}: Check date values in: |date= (help)
  22. ^ a b c d 1.    Sanofi Canada: ZUACTA (zucapsaicin cream) product monograph [Link]
  23. ^ a b c d Bernstein JE. Method and compositions of civamide to treat disease of the intestines. WO2011100668 A4; 2011
  24. ^ Schnitzer TJ, Pelletier JP, Haselwood DM. Civamide cream 0.075% in patients with osteoarthritis of the knee: a 12-week randomized controlled clinical trial with a longterm extension. J Rheumatol 2012;39(3):610-20
  25. ^ https://pubchem.ncbi.nlm.nih.gov/. {{cite web}}: Cite has empty unknown parameter: |dead-url= (help); Missing or empty |title= (help)



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