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{{Drugbox|
{{Drugbox
|IUPAC_name = 2-(2-chlorophenyl)-9-ethyl-6-methyl- 8-thia-3,6-diazabicyclo[5.3.0]deca-2,9,11-trien-5-one
| Verifiedfields = changed
| image = Clotiazepam.svg
| Watchedfields = changed
| image2= Clotiazepam3d.png
| verifiedrevid = 447551242
| width=200
| IUPAC_name = 2-(2-chlorophenyl)-9-ethyl-6-methyl-8-thia-3,6-diazabicyclo[5.3.0]deca-2,9,11-trien-5-one
| CAS_number=33671-46-4
| image = Clotiazepam.png
| ATC_prefix=N05
| width = 200
| ATC_suffix=BA21
| image2 =Clotiazepam3d.png  
| ATC_supplemental=
 
| PubChem=2811
<!--Clinical data-->
| DrugBank=?
| tradename = Veratran, Rize, Clozan
| C=16 | H=15 | Cl=1 | N=2 | O=1 | S=1
| Drugs.com = {{drugs.com|international|clotiazepam}}
| molecular_weight = 318.8 g/mol
| bioavailability= ?
| metabolism = [[Liver|Hepatic]]
| elimination_half-life= ?
| excretion =  [[Kidney|Renal]]
| pregnancy_category = ?
| pregnancy_category = ?
| legal_US = Schedule IV
| legal_US = Schedule IV
| routes_of_administration= Oral
| routes_of_administration = Oral, sublingual, liquid drops 
 
<!--Pharmacokinetic data-->
| bioavailability = ~90%
| metabolism = [[Liver|Hepatic]]
| elimination_half-life = 6-18 hr
| excretion = [[Kidney|Renal]]
 
<!--Identifiers-->
| CASNo_Ref = {{cascite|correct|CAS}}
| CAS_number_Ref = {{cascite|correct|??}}
| CAS_number = 33671-46-4
| ATC_prefix = N05
| ATC_suffix = BA21
| PubChem = 2811
| ChEMBL_Ref = {{ebicite|changed|EBI}}
| ChEMBL = 1697737
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| DrugBank = DB01559
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 2709
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = ZCN055599V
| KEGG_Ref = {{keggcite|correct|kegg}}
| KEGG = D01328
 
<!--Chemical data-->
| C=16 | H=15 | Cl=1 | N=2 | O=1 | S=1
| molecular_weight = 318.8 g/mol
| smiles = ClC1=C(C2=NCC(N(C)C3=C2C=C(CC)S3)=O)C=CC=C1
| InChI = 1/C16H15ClN2OS/c1-3-10-8-12-15(11-6-4-5-7-13(11)17)18-9-14(20)19(2)16(12)21-10/h4-8H,3,9H2,1-2H3
| InChIKey = CHBRHODLKOZEPZ-UHFFFAOYAO
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 1S/C16H15ClN2OS/c1-3-10-8-12-15(11-6-4-5-7-13(11)17)18-9-14(20)19(2)16(12)21-10/h4-8H,3,9H2,1-2H3
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = CHBRHODLKOZEPZ-UHFFFAOYSA-N
}}
}}
'''Clotiazepam''' (marketed under brand name '''Trecalmo''') is a drug which is a [[benzodiazepine]] derivative. It possesses [[anxiolytic]], [[anticonvulsant]], [[sedative]] and [[skeletal muscle relaxant]] properties.
__Notoc__
Stage 2 NREM sleep is significantly increased by clotiazepam.<ref>{{cite journal | author = Nakazawa Y | coauthors = Kotorii M, Oshima M, Horikawa S, Tachibana H. | year = 1975 | month = Oct | date = 31 | title = Effects of thienodiazepine derivatives on human sleep as compared to those of benzodiazepine derivatives. | journal = Psychopharmacologia. | volume = 44 | issue = 2 | pages = 165-71 | pmid = 709 }}</ref>
{{SI}}
{{CMG}}
==Overview==
 
'''Clotiazepam'''<ref>DE Patent 2107356</ref> (marketed under brand name '''Clozan''', '''Distensan''', '''Trecalmo''', '''Rize''', '''Rizen''' and '''Veratran''') is a [[thienodiazepine]] drug which is a [[benzodiazepine]] analog. The clotiazepam molecule differs from most other benzodiazepines in that the benzene ring has been replaced by a [[thiophene]] ring.<ref>{{cite journal |author=Niwa T, Shiraga T, Ishii I, Kagayama A, Takagi A |title=Contribution of human hepatic cytochrome p450 isoforms to the metabolism of psychotropic drugs |journal=Biol. Pharm. Bull. |volume=28 |issue=9 |pages=1711–6 |date=September 2005 |pmid=16141545 |doi= 10.1248/bpb.28.1711|url=http://www.jstage.jst.go.jp/article/bpb/28/9/1711/_pdf |format=PDF|last2=Shiraga |last3=Ishii |last4=Kagayama |last5=Takagi }}</ref> It possesses [[anxiolytic]],<ref name="Klicpera-1978">{{Cite journal | last1 = Klicpera | first1 = C. | last2 = Strian | first2 = F. | title = Autonomic perception and responses in anxiety-inducing situations. | journal = Pharmakopsychiatr Neuropsychopharmakol | volume = 11 | issue = 3 | pages = 113–20 |date=May 1978 | doi = 10.1055/s-0028-1094569 | pmid = 27828 }}</ref> [[skeletal muscle relaxant]],<ref name="Fukuda-1983">{{Cite journal | last1 = Fukuda | first1 = T. | last2 = Tsumagari | first2 = T. | title = Effects of psychotropic drugs on the rage responses induced by electrical stimulation of the medial hypothalamus in cats. | url = http://www.journalarchive.jst.go.jp/jnlpdf.php?cdjournal=jphs1951&cdvol=33&noissue=4&startpage=885&lang=en&from=jnlabstract | format = PDF | journal = Jpn J Pharmacol | volume = 33 | issue = 4 | pages = 885–90 |date=Aug 1983 | doi =  10.1254/jjp.33.885| pmid = 6632385 }}</ref> [[anticonvulsant]], [[sedative]] properties.<ref name="Mandrioli-2008">{{Cite journal | last1 = Mandrioli | first1 = R. | last2 = Mercolini | first2 = L. | last3 = Raggi | first3 = MA. | title = Benzodiazepine metabolism: an analytical perspective. | journal = Curr Drug Metab | volume = 9 | issue = 8 | pages = 827–44 |date=Oct 2008 | doi =  10.2174/138920008786049258| pmid = 18855614 }}</ref> Stage 2 [[NREM]] sleep is significantly increased by clotiazepam.<ref>{{cite journal | author = Nakazawa Y |author2=Kotorii M|author3=Oshima M|author4=Horikawa S|author5=Tachibana H. | date = October 31, 1975 | title = Effects of thienodiazepine derivatives on human sleep as compared to those of benzodiazepine derivatives. | journal = Psychopharmacologia. | volume = 44 | issue = 2 | pages = 165–71 | pmid = 709 | doi = 10.1007/BF00421005 }}</ref>
 
==Indications==
Clotiazepam has been trialed and found to be effective in the short-term management of [[anxiety]].<ref name="Martucci-1987">{{Cite journal | last1 = Martucci | first1 = N. | last2 = Manna | first2 = V. | last3 = Agnoli | first3 = A. | title = A clinical and neurophysiological evaluation of clotiazepam, a new thienodiazepine derivative. | journal = Int Clin Psychopharmacol | volume = 2 | issue = 2 | pages = 121–8 |date=Apr 1987 | doi =  10.1097/00004850-198704000-00005| pmid = 2885366 }}</ref> Clotiazepam is also used as a premedicant in minor surgery in [[France]] and [[Japan]], where the drug is commercially available under the brand names ''Veratran'' and ''Rize'', respectively.<ref name=RIZE>[http://di.mt-pharma.co.jp/file/shiori/s_riz_d_e.doc Official Japanese Drug Information Sheet (Kusuri-no-Shiori)]</ref><ref name=VRTN>[http://www.doctissimo.fr/medicament-VERATRAN.htm French Guide to Medicines - Clotiazepam (Veratran)]</ref>
 
==Pharmacokinetics==
A cross-over study in six healthy volunteers (median age 28 years) was conducted using single-dose pharmacokinetics of 5&nbsp;mg clotiazepam [[Drop (unit)|drops]], [[Tablet (pharmacy)|oral tablets]], and [[Sublingual administration|sublingual tablets]]. The formulations had similar systemic availability. Compared with oral tablets, the sublingual route gave a lower peak concentration and a delayed peak time, while drops gave a greater maximum concentration with a similar peak time. The use of drops is suggested for a more marked initial effect and the sublingual route for easier administration, especially in the elderly.<ref name="PHKTS">{{Cite journal | title = The pharmacokinetics of clotiazepam after oral and sublingual administration to volunteers | journal = European Journal of Clinical Pharmacology | volume = 37 | issue = 6 | pages = 617–619 | year = 1989 | doi =  10.1007/BF00562556 | url=http://resources.metapress.com/pdf-preview.axd?code=v72413q7v4781472&size=largest | author = C. Benvenuti, V. Bottà, M. Broggini, V. Gambaro, F. Lodi and M. Valenti | pmid = 2575522| doi_brokendate = 2015-01-11 }}</ref>
 
==Pharmacology==
Similar to other benzodiazepines clotiazepam has [[anxiolytic]], [[sedative]], [[hypnotic]], [[amnesic]], [[anticonvulsant]] and [[muscle relaxant]] pharmacological properties.<ref name="Mandrioli-2008"/> Clotiazepam binds to the benzodiazepine site of the GABA<sub>A</sub> receptor where it acts as a full agonist; this action results in an enhanced GABA inhibitory effect at the GABA<sub>A</sub> receptor which results in the pharmacological effects of clotiazepam.<ref name="Yakushiji-1989">{{Cite journal | last1 = Yakushiji | first1 = T. | last2 = Fukuda | first2 = T. | last3 = Oyama | first3 = Y. | last4 = Akaike | first4 = N. | title = Effects of benzodiazepines and non-benzodiazepine compounds on the GABA-induced response in frog isolated sensory neurones | format = PDF | journal = Br J Pharmacol | volume = 98 | issue = 3 | pages = 735–40 |date=Nov 1989 | doi =  10.1111/j.1476-5381.1989.tb14600.x| pmid=2574062 | pmc=1854765}}</ref>
 
Clotiazepam has a relatively short [[elimination half-life]] and is less prone to accumulation after repeated dosing compared to longer-acting benzodiazepine agents. It is metabolised via oxidation.<ref name="Greenblatt-">{{Cite journal | last1 = Greenblatt | first1 = DJ. | last2 = Divoll | first2 = M. | last3 = Abernethy | first3 = DR. | last4 = Ochs | first4 = HR. | last5 = Shader | first5 = RI. | title = Clinical pharmacokinetics of the newer benzodiazepines | journal = Clin Pharmacokinet | volume = 8 | issue = 3 | pages = 233–52 | year =  1983| doi =  10.2165/00003088-198308030-00003| pmid = 6133664 }}</ref> Clotiazepam is metabolised to hydroxy-clotiazepam and desmethyl-clotiazepam. After oral ingestion of a single 5&nbsp;mg dose of clotiazepam by three healthy volunteers the drug was rapidly absorbed.<ref name="Arendt-1982"/> The elimination half-life of the drug and its metabolites range from 6.5 hours to 18 hours. Clotiazepam is 99 percent bound to plasma protein.<ref name="Arendt-1982">{{Cite journal | last1 = Arendt | first1 = R. | last2 = Ochs | first2 = HR. | last3 = Greenblatt | first3 = DJ. | title = Electron capture GLC analysis of the thienodiazepine clotiazepam. Preliminary pharmacokinetic studies | journal = Arzneimittelforschung | volume = 32 | issue = 4 | pages = 453–5 | year = 1982 | doi =  | pmid = 6125154 }}</ref> In elderly men the elimination half-life is longer and in elderly women the volume of distribution is increased.<ref name="Ochs-1984">{{Cite journal | last1 = Ochs | first1 = HR. | last2 = Greenblatt | first2 = DJ. | last3 = Verburg-Ochs | first3 = B. | last4 = Harmatz | first4 = JS. | last5 = Grehl | first5 = H. | title = Disposition of clotiazepam: influence of age, sex, oral contraceptives, cimetidine, isoniazid and ethanol | journal = Eur J Clin Pharmacol | volume = 26 | issue = 1 | pages = 55–9 | year = 1984 | doi =  10.1007/BF00546709| pmid = 6143670 }}</ref> Individuals with liver impairment have a reduced volume of distribution as well as a reduced total clearance of clotiazepam; renal impairment does not affect the kinetics of clotiazepam.<ref name="Ochs-1986">{{Cite journal | last1 = Ochs | first1 = HR. | last2 = Greenblatt | first2 = DJ. | last3 = Knüchel | first3 = M. | title = Effect of cirrhosis and renal failure on the kinetics of clotiazepam | journal = Eur J Clin Pharmacol | volume = 30 | issue = 1 | pages = 89–92 | year = 1986 | doi =  10.1007/BF00614202| pmid = 2872061 }}</ref>
 
==Side effects==
[[Drowsiness]] and [[asthenia]] are common side effects.<ref name="Colonna-">{{Cite journal  | last1 = Colonna | first1 = L. | last2 = Cozzi | first2 = F. | last3 = Del Citerna | first3 = F. | last4 = Di Benedetto | first4 = A. | last5 = De Divitiis | first5 = O. | last6 = Furlanello | first6 = F. | last7 = Milazzotto | first7 = F. | last8 = Pittalis | first8 = M. | last9 = Taccola | first9 = A. | title = [Multicenter study of the effectiveness and tolerance of clotiazepam in cardiology] | journal = Minerva Cardioangiol | volume = 38 | issue = 1–2 | pages = 45–9 | year =  1990| doi =  | pmid = 1971433  }}</ref> There has been a report of [[hepatitis]] caused by clotiazepam.<ref name="Habersetzer-1989">{{Cite journal  | last1 = Habersetzer | first1 = F. | last2 = Larrey | first2 = D. | last3 = Babany | first3 = G. | last4 = Degott | first4 = C. | last5 = Corbic | first5 = M. | last6 = Pessayre | first6 = D. | last7 = Benhamou | first7 = JP. | title = Clotiazepam-induced acute hepatitis | journal = J Hepatol | volume = 9 | issue = 2 | pages = 256–9 |date=Sep 1989 | doi =  10.1016/0168-8278(89)90060-3| pmid = 2572625 }}</ref>
 
==Abuse==
Clotiazepam is a recognised drug of abuse.<ref name="Shimamine-1993">{{Cite journal | last1 = Shimamine | first1 = M. | last2 = Masunari | first2 = T. | last3 = Nakahara | first3 = Y. | title = [Studies on identification of drugs of abuse by diode array detection. I. Screening-test and identification of benzodiazepines by HPLC-DAD with ICOS software system] | journal = Eisei Shikenjo Hokoku | volume =  | issue = 111 | pages = 47–56 | year = 1993 | doi =  | pmid = 7920567 }}</ref>
 
==See also==
*[[List of benzodiazepines]]
*[[Etizolam]]


Clotiazepam is not approved for sale in the United States or Canada.
==References==
==References==
<div class="references-2column">
{{reflist|2}}
<references/>
</div>


==External links==
==External links==
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{{Benzodiazepines}}
{{Benzodiazepines}}
{{Anxiolytics}}
{{GABAAR PAMs}}


[[Category:Benzodiazepines]]
[[Category:Drug]]
[[Category:Hypnotics]]
[[Category:Thienodiazepines]]
 
[[Category:Lactams]]
 
[[Category:Organochlorides]]
{{psychoactive-stub}}
[[Category:GABAA receptor positive allosteric modulators]]
 
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Latest revision as of 14:31, 9 April 2015

Clotiazepam
Clinical data
Trade namesVeratran, Rize, Clozan
AHFS/Drugs.comInternational Drug Names
Pregnancy
category
  • ?
Routes of
administration		Oral, sublingual, liquid drops
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability~90%
MetabolismHepatic
Elimination half-life6-18 hr
ExcretionRenal
Identifiers
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEMBL
E number{{#property:P628}}
ECHA InfoCard{{#property:P2566}}Lua error in Module:EditAtWikidata at line 36: attempt to index field 'wikibase' (a nil value).
Chemical and physical data
FormulaC16H15ClN2OS
Molar mass318.8 g/mol
3D model (JSmol)
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Overview

Clotiazepam[1] (marketed under brand name Clozan, Distensan, Trecalmo, Rize, Rizen and Veratran) is a thienodiazepine drug which is a benzodiazepine analog. The clotiazepam molecule differs from most other benzodiazepines in that the benzene ring has been replaced by a thiophene ring.[2] It possesses anxiolytic,[3] skeletal muscle relaxant,[4] anticonvulsant, sedative properties.[5] Stage 2 NREM sleep is significantly increased by clotiazepam.[6]

Indications

Clotiazepam has been trialed and found to be effective in the short-term management of anxiety.[7] Clotiazepam is also used as a premedicant in minor surgery in France and Japan, where the drug is commercially available under the brand names Veratran and Rize, respectively.[8][9]

Pharmacokinetics

A cross-over study in six healthy volunteers (median age 28 years) was conducted using single-dose pharmacokinetics of 5 mg clotiazepam drops, oral tablets, and sublingual tablets. The formulations had similar systemic availability. Compared with oral tablets, the sublingual route gave a lower peak concentration and a delayed peak time, while drops gave a greater maximum concentration with a similar peak time. The use of drops is suggested for a more marked initial effect and the sublingual route for easier administration, especially in the elderly.[10]

Pharmacology

Similar to other benzodiazepines clotiazepam has anxiolytic, sedative, hypnotic, amnesic, anticonvulsant and muscle relaxant pharmacological properties.[5] Clotiazepam binds to the benzodiazepine site of the GABAA receptor where it acts as a full agonist; this action results in an enhanced GABA inhibitory effect at the GABAA receptor which results in the pharmacological effects of clotiazepam.[11]

Clotiazepam has a relatively short elimination half-life and is less prone to accumulation after repeated dosing compared to longer-acting benzodiazepine agents. It is metabolised via oxidation.[12] Clotiazepam is metabolised to hydroxy-clotiazepam and desmethyl-clotiazepam. After oral ingestion of a single 5 mg dose of clotiazepam by three healthy volunteers the drug was rapidly absorbed.[13] The elimination half-life of the drug and its metabolites range from 6.5 hours to 18 hours. Clotiazepam is 99 percent bound to plasma protein.[13] In elderly men the elimination half-life is longer and in elderly women the volume of distribution is increased.[14] Individuals with liver impairment have a reduced volume of distribution as well as a reduced total clearance of clotiazepam; renal impairment does not affect the kinetics of clotiazepam.[15]

Side effects

Drowsiness and asthenia are common side effects.[16] There has been a report of hepatitis caused by clotiazepam.[17]

Abuse

Clotiazepam is a recognised drug of abuse.[18]

See also

References

  1. ↑ DE Patent 2107356
  2. ↑ Niwa T, Shiraga T, Ishii I, Kagayama A, Takagi A; Shiraga; Ishii; Kagayama; Takagi (September 2005). "Contribution of human hepatic cytochrome p450 isoforms to the metabolism of psychotropic drugs" (PDF). Biol. Pharm. Bull. 28 (9): 1711–6. doi:10.1248/bpb.28.1711. PMID 16141545.
  3. ↑ Klicpera, C.; Strian, F. (May 1978). "Autonomic perception and responses in anxiety-inducing situations". Pharmakopsychiatr Neuropsychopharmakol. 11 (3): 113–20. doi:10.1055/s-0028-1094569. PMID 27828.
  4. ↑ Fukuda, T.; Tsumagari, T. (Aug 1983). "Effects of psychotropic drugs on the rage responses induced by electrical stimulation of the medial hypothalamus in cats" (PDF). Jpn J Pharmacol. 33 (4): 885–90. doi:10.1254/jjp.33.885. PMID 6632385.
  5. ↑ 5.0 5.1 Mandrioli, R.; Mercolini, L.; Raggi, MA. (Oct 2008). "Benzodiazepine metabolism: an analytical perspective". Curr Drug Metab. 9 (8): 827–44. doi:10.2174/138920008786049258. PMID 18855614.
  6. ↑ Nakazawa Y; Kotorii M; Oshima M; Horikawa S; Tachibana H. (October 31, 1975). "Effects of thienodiazepine derivatives on human sleep as compared to those of benzodiazepine derivatives". Psychopharmacologia. 44 (2): 165–71. doi:10.1007/BF00421005. PMID 709.
  7. ↑ Martucci, N.; Manna, V.; Agnoli, A. (Apr 1987). "A clinical and neurophysiological evaluation of clotiazepam, a new thienodiazepine derivative". Int Clin Psychopharmacol. 2 (2): 121–8. doi:10.1097/00004850-198704000-00005. PMID 2885366.
  8. ↑ Official Japanese Drug Information Sheet (Kusuri-no-Shiori)
  9. ↑ French Guide to Medicines - Clotiazepam (Veratran)
  10. ↑ C. Benvenuti, V. Bottà, M. Broggini, V. Gambaro, F. Lodi and M. Valenti (1989). "The pharmacokinetics of clotiazepam after oral and sublingual administration to volunteers". European Journal of Clinical Pharmacology. 37 (6): 617–619. doi:10.1007/BF00562556. PMID 2575522. Unknown parameter |doi_brokendate= ignored (help)
  11. ↑ Yakushiji, T.; Fukuda, T.; Oyama, Y.; Akaike, N. (Nov 1989). "Effects of benzodiazepines and non-benzodiazepine compounds on the GABA-induced response in frog isolated sensory neurones" (PDF). Br J Pharmacol. 98 (3): 735–40. doi:10.1111/j.1476-5381.1989.tb14600.x. PMC 1854765. PMID 2574062.
  12. ↑ Greenblatt, DJ.; Divoll, M.; Abernethy, DR.; Ochs, HR.; Shader, RI. (1983). "Clinical pharmacokinetics of the newer benzodiazepines". Clin Pharmacokinet. 8 (3): 233–52. doi:10.2165/00003088-198308030-00003. PMID 6133664.
  13. ↑ 13.0 13.1 Arendt, R.; Ochs, HR.; Greenblatt, DJ. (1982). "Electron capture GLC analysis of the thienodiazepine clotiazepam. Preliminary pharmacokinetic studies". Arzneimittelforschung. 32 (4): 453–5. PMID 6125154.
  14. ↑ Ochs, HR.; Greenblatt, DJ.; Verburg-Ochs, B.; Harmatz, JS.; Grehl, H. (1984). "Disposition of clotiazepam: influence of age, sex, oral contraceptives, cimetidine, isoniazid and ethanol". Eur J Clin Pharmacol. 26 (1): 55–9. doi:10.1007/BF00546709. PMID 6143670.
  15. ↑ Ochs, HR.; Greenblatt, DJ.; Knüchel, M. (1986). "Effect of cirrhosis and renal failure on the kinetics of clotiazepam". Eur J Clin Pharmacol. 30 (1): 89–92. doi:10.1007/BF00614202. PMID 2872061.
  16. ↑ Colonna, L.; Cozzi, F.; Del Citerna, F.; Di Benedetto, A.; De Divitiis, O.; Furlanello, F.; Milazzotto, F.; Pittalis, M.; Taccola, A. (1990). "[Multicenter study of the effectiveness and tolerance of clotiazepam in cardiology]". Minerva Cardioangiol. 38 (1–2): 45–9. PMID 1971433.
  17. ↑ Habersetzer, F.; Larrey, D.; Babany, G.; Degott, C.; Corbic, M.; Pessayre, D.; Benhamou, JP. (Sep 1989). "Clotiazepam-induced acute hepatitis". J Hepatol. 9 (2): 256–9. doi:10.1016/0168-8278(89)90060-3. PMID 2572625.
  18. ↑ Shimamine, M.; Masunari, T.; Nakahara, Y. (1993). "[Studies on identification of drugs of abuse by diode array detection. I. Screening-test and identification of benzodiazepines by HPLC-DAD with ICOS software system]". Eisei Shikenjo Hokoku (111): 47–56. PMID 7920567.

External links

Template:Benzodiazepines Template:Anxiolytics Template:GABAAR PAMs

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