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{{Short description|Pharmaceutical drug}} |
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{{Drugbox |
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{{Drugbox |
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| verifiedrevid = 449585706 |
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| IUPAC_name = 5-(3-propoxy)-1,3-benzodioxole |
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| verifiedrevid = 451554517 |
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| image = Osemozotan.png |
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| IUPAC_name = 5-(3-propoxy)-1,3-benzodioxole |
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| image = Osemozotan.svg |
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<!--Clinical data--> |
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<!--Clinical data-->| tradename = |
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| tradename = |
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| pregnancy_category = |
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| legal_status = Uncontrolled |
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| pregnancy_category = |
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| routes_of_administration = <!--Pharmacokinetic data--> |
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| legal_status = Uncontrolled |
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| bioavailability = |
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| routes_of_administration = |
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| metabolism = |
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| elimination_half-life = |
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| excretion = <!--Identifiers--> |
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| CAS_number_Ref = {{cascite|correct|CAS}} |
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| CAS_number = 137275-81-1 |
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| ATC_prefix = |
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| PubChem = 198746 |
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| ChemSpiderID_Ref = {{chemspidercite|changed|chemspider}} |
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| UNII_Ref = {{fdacite|correct|FDA}} |
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| UNII = M65825806Q |
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| ChemSpiderID = 172023 |
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| index2_label = HCl |
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| CAS_number2_Ref = {{cascite|correct|CAS}} |
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| CAS_number2 = 137275-80-0 |
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| UNII2_Ref = {{fdacite|correct|FDA}} |
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| UNII2 = F0WKFYPQL8 |
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<!--Chemical data-->| C = 19 |
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| H = 21 |
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| N = 1 |
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| O = 5 |
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| smiles = C1(OC2=CC=CC=C2O1)CNCCCOC3=CC4=C(C=C3)OCO4 |
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| StdInChI_Ref = {{stdinchicite|changed|chemspider}} |
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| StdInChI = 1S/C19H21NO5/c1-2-5-18-16(4-1)22-12-15(25-18)11-20-8-3-9-21-14-6-7-17-19(10-14)24-13-23-17/h1-2,4-7,10,15,20H,3,8-9,11-13H2/t15-/m0/s1 |
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| StdInChIKey_Ref = {{stdinchicite|changed|chemspider}} |
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| StdInChIKey = MEEQBDCQPIZMLY-HNNXBMFYSA-N |
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}} |
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'''Osemozotan''' ('''MKC-242''') is a ] ] ] with some ], acting as a ] at presynaptic and a ] at postsynaptic 5-HT<sub>1A</sub> receptors.<ref name="pmid8786639"/> 5-HT<sub>1A</sub> receptor stimulation influences the release of various ]s including ], ], ], and ].<ref name= "Main">{{cite journal | vauthors = Matsuda T | title = Neuropharmacologic studies on the brain serotonin1A receptor using the selective agonist osemozotan | journal = Biological & Pharmaceutical Bulletin | volume = 36 | issue = 12 | pages = 1871–82 | date = 2013 | pmid = 24292048 | doi = 10.1248/bpb.b13-00645 | doi-access = free }}</ref> 5-HT<sub>1A</sub> receptors are inhibitory ].<ref name="pmid7894328">{{cite journal | vauthors = Saudou F, Hen R | title = 5-Hydroxytryptamine receptor subtypes in vertebrates and invertebrates | journal = Neurochemistry International | volume = 25 | issue = 6 | pages = 503–32 | date = December 1994 | pmid = 7894328 | doi = 10.1016/0197-0186(94)90150-3 | s2cid = 34436470 }}</ref> |
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<!--Pharmacokinetic data--> |
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| bioavailability = |
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Osemozotan has been shown in animal studies to have ], ], ], ], and ] effects.<ref>{{cite journal | vauthors = Abe M, Tabata R, Saito K, Matsuda T, Baba A, Egawa M | title = Novel benzodioxan derivative, 5-propoxy]-1,3-benzodioxole HCl (MKC-242), with anxiolytic-like and antidepressant-like effects in animal models | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 278 | issue = 2 | pages = 898–905 | date = August 1996 | pmid = 8768745 }}</ref><ref>{{cite journal | vauthors = Sakaue M, Ago Y, Sowa C, Koyama Y, Baba A, Matsuda T | title = The 5-HT1A receptor agonist MKC-242 increases the exploratory activity of mice in the elevated plus-maze | journal = European Journal of Pharmacology | volume = 458 | issue = 1–2 | pages = 141–4 | date = January 2003 | pmid = 12498918 | doi = 10.1016/S0014-2999(02)02786-3 }}</ref><ref name="Marbles">Abe, Michikazu, Hiroshi Nakai, Reiko Tabata, Ken-Ichi Saito, and Mitsuo Egawa. "Effect of 5-{3-propoxy}-1,3-benzodioxole HCL (MKC-242), a Novel 5-HT1A-Receptor Agonist, on Aggressive Behavior and Marble Burying Behavior in Mice." ''Jpn. J. Pharmacol.'' '''76''' (1998): 297-304.</ref><ref name="Main" /> It is used to investigate the role of 5-HT<sub>1A</sub> receptors in modulating the release of ] and ] in the brain<ref>{{cite journal | vauthors = Sakaue M, Somboonthum P, Nishihara B, Koyama Y, Hashimoto H, Baba A, Matsuda T | title = Postsynaptic 5-hydroxytryptamine(1A) receptor activation increases in vivo dopamine release in rat prefrontal cortex | journal = British Journal of Pharmacology | volume = 129 | issue = 5 | pages = 1028–34 | date = March 2000 | pmid = 10696105 | pmc = 1571922 | doi = 10.1038/sj.bjp.0703139 }}</ref><ref>{{cite journal | vauthors = Ago Y, Koyama Y, Baba A, Matsuda T | title = Regulation by 5-HT1A receptors of the in vivo release of 5-HT and DA in mouse frontal cortex | journal = Neuropharmacology | volume = 45 | issue = 8 | pages = 1050–6 | date = December 2003 | pmid = 14614948 | doi = 10.1016/S0028-3908(03)00304-6 | s2cid = 20463997 }}</ref> and their involvement in addiction to stimulants such as cocaine and ].<ref name="pmid16863654" /><ref name="pmid16962650" /><ref>{{cite journal | vauthors = Ago Y, Nakamura S, Baba A, Matsuda T | title = Neuropsychotoxicity of abused drugs: effects of serotonin receptor ligands on methamphetamine- and cocaine-induced behavioral sensitization in mice | journal = Journal of Pharmacological Sciences | volume = 106 | issue = 1 | pages = 15–21 | date = January 2008 | pmid = 18198473 | doi = 10.1254/jphs.FM0070121 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Tsuchida R, Kubo M, Kuroda M, Shibasaki Y, Shintani N, Abe M, Köves K, Hashimoto H, Baba A | display-authors = 6 | title = An antihyperkinetic action by the serotonin 1A-receptor agonist osemozotan co-administered with psychostimulants or the non-stimulant atomoxetine in mice | journal = Journal of Pharmacological Sciences | volume = 109 | issue = 3 | pages = 396–402 | date = March 2009 | pmid = 19270432 | doi = 10.1254/jphs.08297FP | doi-access = free }}</ref><ref>{{cite journal | vauthors = Tsuchida R, Kubo M, Shintani N, Abe M, Köves K, Uetsuki K, Kuroda M, Hashimoto H, Baba A | display-authors = 6 | title = Inhibitory effects of osemozotan, a serotonin 1A-receptor agonist, on methamphetamine-induced c-Fos expression in prefrontal cortical neurons | journal = Biological & Pharmaceutical Bulletin | volume = 32 | issue = 4 | pages = 728–31 | date = April 2009 | pmid = 19336914 | doi = 10.1248/bpb.32.728 | doi-access = free }}</ref> |
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<!--Identifiers--> |
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| CAS_number = 137275-80-0 |
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| ATC_prefix = |
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| ATC_suffix = |
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| PubChem = 198746 |
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| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} |
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| ChemSpiderID = |
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| UNII_Ref = {{fdacite|correct|FDA}} |
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| UNII = M65825806Q |
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==Pharmacodynamics== |
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<!--Chemical data--> |
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The binding target of Osemozotan is 5-HT<sub>1A</sub> receptors. Osemozotan binds with almost 1000 times greater affinity to 5-HT<sub>1A</sub> receptors than to most other 5-HT, dopamine, or adrenergic receptors.<ref name= "Main"/> Even with repeated exposure of 5-HT<sub>1A</sub> receptors to Osemozotan, there is no change in the number of receptors, unlike with other ] ]s.<ref name="pmid9195299">{{cite journal | vauthors = Asano S, Matsuda T, Yoshikawa T, Somboonthum P, Tasaki H, Abe M, Baba A | title = Interaction of orally administered 5-propoxy]-1,3-benzodioxole (MKC-242) with 5-HT1A receptors in rat brain | journal = Japanese Journal of Pharmacology | volume = 74 | issue = 1 | pages = 69–75 | date = May 1997 | pmid = 9195299 | doi = 10.1254/jjp.74.69 | doi-access = free }}</ref> |
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| C=20 | H=23 | N=1 | O=4 |
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| molecular_weight = 341.400 g/mol |
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| smiles = c4cc1OCOc1cc4OCCCNCC3CCc2ccccc2O3 |
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}} |
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==Pharmacokinetics== |
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'''Osemozotan''' ('''MKC-242''') is a ] ] ] with some ], acting as a ] at presynaptic and a ] at postsynaptic 5-HT<sub>1A</sub> receptors.<ref>{{Cite pmid|8786639}}</ref> It has ] and ] effects in animal studies,<ref>{{Cite pmid|8768745}}</ref><ref>{{Cite pmid|12498918}}</ref> and is used to investigate the role of 5-HT<sub>1A</sub> receptors in modulating the release of ] and ] in the brain,<ref>{{Cite pmid|10696105}}</ref><ref>{{Cite pmid|14614948}}</ref> and their involvement in addiction to abused stimulants such as cocaine and methamphetamine.<ref>{{Cite pmid|16863654}}</ref><ref>{{Cite pmid|16962650}}</ref><ref>{{Cite pmid|18198473}}</ref><ref>{{Cite pmid|19270432}}</ref><ref>{{Cite pmid|19336914}}</ref> |
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Pharmacokinetic data collected from animal studies performed in mice and rats revealed an oral ] of 15 minutes, an ] of 2.943 mg·hr·L<sup>−1</sup> and a ] of 1.3 hours.<ref name= "Marbles" /> Pharmacokinetic testing has been able to help explain the longer acting pharmacologic effects of Osemozotan as well as its increased potency. Osemozotan was shown to have increased duration of pharmacologic effects compared to ]s and requires a substantially lower dose to produce its pharmacologic effects.<ref name= "Marbles"/> This result suggests that patients may not have to take the medication as often throughout the day. In these studies, there was a difference in dosage amount required for the intended indication.<ref name= "Marbles" /> Osemozotan does not metabolize to ], a common metabolite found with the azapirone class of medications that has affinity for receptors other than 5-HT<sub>1A</sub>, thus decreasing its specificity and increasing the risk of unwanted effects.<ref name= "Marbles" /> Since Osemozotan does not produce this metabolite, it has greater specificity toward 5-HT<sub>1A</sub> when compared to other anxiolytic medications. |
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==Uses== |
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Osemozotan is being investigated for use in treating pain, aggressive behavior, anxiety, depression, ], and dependence on methamphetamine and cocaine.<ref name= "Main" /><ref name= "Marbles" /> |
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===Pain=== |
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It has been proposed that Osemozotan could be used as an analgesic agent because of its activation of 5-HT<sub>1A</sub> receptors associated with an inhibitory serotonin-signaling pathway within the spinal cord which causes ] and decreasing mechanical ].<ref name= "Main" /><ref name="pmid24161684">{{cite journal | vauthors = Horiguchi N, Ago Y, Hasebe S, Higashino K, Asada K, Kita Y, Takuma K, Matsuda T | display-authors = 6 | title = Isolation rearing reduces mechanical allodynia in a mouse model of chronic inflammatory pain | journal = Pharmacology, Biochemistry, and Behavior | volume = 113 | pages = 46–52 | date = November 2013 | pmid = 24161684 | doi = 10.1016/j.pbb.2013.10.017 | s2cid = 19975118 }}</ref> |
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===Aggressive behavior=== |
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Osemozotan was found to decrease the incidence of fighting in mice similar to ], ], and ] but required a lower pharmacologic dose to produce beneficial effects.<ref name= "Marbles" /> Osemozotan showed dose-dependent anti-aggressive effects and was not shown to decrease motor coordination in the mice.<ref name= "Marbles"/> |
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===Anxiety and depression=== |
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When stimulated, 5-HT<sub>1A</sub> receptors are shown to have anxiolytic and antidepressant pharmacologic effects.<ref name= "Main" /> |
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===Obsessive-compulsive disorder=== |
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OCD patients have been found to have increased 5-HT levels in the brain.<ref name="pmid8786639">{{cite journal | vauthors = Matsuda T, Yoshikawa T, Suzuki M, Asano S, Somboonthum P, Takuma K, Nakano Y, Morita T, Nakasu Y, Kim HS | display-authors = 6 | title = Novel benzodioxan derivative, 5-(3-propoxy)-1,3-benzodioxole HCl (MKC-242), with a highly potent and selective agonist activity at rat central serotonin1A receptors | journal = Japanese Journal of Pharmacology | volume = 69 | issue = 4 | pages = 357–66 | date = December 1995 | pmid = 8786639 | doi = 10.1254/jjp.69.357 | doi-access = free }}</ref><ref name="pmid2439924">{{cite journal | vauthors = McMillen BA, Scott SM, Williams HL, Sanghera MK | title = Effects of gepirone, an aryl-piperazine anxiolytic drug, on aggressive behavior and brain monoaminergic neurotransmission | journal = Naunyn-Schmiedeberg's Archives of Pharmacology | volume = 335 | issue = 4 | pages = 454–64 | date = April 1987 | pmid = 2439924 | doi = 10.1007/bf00165563 | s2cid = 23396992 }}</ref> With the use of Osemozotan as a 5-HT<sub>1A</sub> agonist, there is a decrease in serotonergic activity in the brain, leading to possible anti-obsessional pharmacological action.<ref name= "Marbles" /> One animal mouse model used to test for OCD is known as the marble burying test, in which the amount of marbles buried within a certain time frame is recorded.<ref name= "Marbles" /> Mice performed the marble burying test both with and without Osemozotan. With Osemozotan administration, the number of marbles buried was decreased with apparently little to no loss in motor coordination; these test results support the theory that Osemozotan may be useful in the treatment of OCD.<ref name= "Marbles" /> |
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===Drug dependence=== |
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It has been noted that ] to cocaine may stem from action of the 5-HT<sub>1A </sub>receptor.<ref name="pmid16962650">{{cite journal | vauthors = Ago Y, Nakamura S, Hayashi A, Itoh S, Baba A, Matsuda T | title = Effects of osemozotan, ritanserin and azasetron on cocaine-induced behavioral sensitization in mice | journal = Pharmacology, Biochemistry, and Behavior | volume = 85 | issue = 1 | pages = 198–205 | date = September 2006 | pmid = 16962650 | doi = 10.1016/j.pbb.2006.07.036 | s2cid = 1794862 }}</ref><ref name="pmid16952156">{{cite journal | vauthors = Nakamura S, Ago Y, Hayashi A, Itoh S, Kakuda M, Hashimoto H, Baba A, Matsuda T | display-authors = 6 | title = Modification of cocaine-induced behavioral and neurochemical effects by serotonin1A receptor agonist/antagonist in mice | journal = Synapse | volume = 60 | issue = 7 | pages = 479–84 | date = December 2006 | pmid = 16952156 | doi = 10.1002/syn.20323 | s2cid = 29597138 }}</ref> While the role of 5-HT receptors with methamphetamine is still not certain, the use of Osemozotan was found to decrease 5-HT levels in patients on repeated methamphetamine exposure; this may be a possibility for treatment of drug dependence with cocaine and methamphetamine.<ref name="pmid16863654">{{cite journal | vauthors = Ago Y, Nakamura S, Uda M, Kajii Y, Abe M, Baba A, Matsuda T | title = Attenuation by the 5-HT1A receptor agonist osemozotan of the behavioral effects of single and repeated methamphetamine in mice | journal = Neuropharmacology | volume = 51 | issue = 4 | pages = 914–22 | date = September 2006 | pmid = 16863654 | doi = 10.1016/j.neuropharm.2006.06.001 | s2cid = 38888234 }}</ref> |
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==Prevalence of mental disease states== |
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About 18% of American adults suffer from some type of anxiety disorder, <ref>{{Cite web | url=http://www.adaa.org/about-adaa/press-room/facts-statistics | title=Facts & Statistics | Anxiety and Depression Association of America, ADAA}}</ref> and 1 in 5 adults in the United States are on some type of medication to help control or improve their behavior.<ref name= "USA">{{Cite web | url=http://usatoday30.usatoday.com/news/health/healthcare/health/healthcare/story/2011-11-16/Report-1-in-5-of-US-adults-on-behavioral-meds/51241236/1 | title=Report: 1 in 5 of U.S. Adults on behavioral meds}}</ref> The prevalence of prescription medication use for mental illnesses has noticeably increased in the past few years,{{when|date=October 2024}} particularly in younger adults and in men.<ref name= "USA" /> Around 60 billion dollars are spent annually for treatments dealing with mental illnesses.<ref>{{Cite web | url=http://www.nimh.nih.gov/health/statistics/cost/mental-healthcare-cost-data-for-all-americans-2006.shtml | title=NIMH » Statistics}}</ref> |
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== See also == |
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== See also == |
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== References == |
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== References == |
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{{Reflist}} |
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{{Serotonergics}} |
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{{Serotonergics}} |
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