| Revision as of 14:07, 5 December 2011 editBeetstra (talk | contribs)Edit filter managers, Administrators172,071 edits Saving copy of the {{drugbox}} taken from revid 456613703 of page Pravadoline for the Chem/Drugbox validation project (updated: 'CAS_number'). |
Latest revision as of 23:41, 10 January 2025 edit Arthurfragoso (talk | contribs)Extended confirmed users, Template editors4,591 edits dark mode fix |
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{{Short description|Chemical compound}} |
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{{ambox | text = This page contains a copy of the infobox ({{tl|drugbox}}) taken from revid of page ] with values updated to verified values.}} |
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{{Drugbox |
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{{Drugbox |
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⚫ |
| verifiedrevid = 464213342 |
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| Watchedfields = changed |
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| IUPAC_name = (4-Methoxyphenyl)-methanone |
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| verifiedrevid = 408966788 |
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| IUPAC_name = (4-methoxyphenyl)-methanone |
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| image = Pravadoline.svg |
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| image = Pravadoline.svg |
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| image_class = skin-invert-image |
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<!--Clinical data--> |
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<!--Clinical data--> |
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| legal_US = <!-- OTC / Rx-only / Schedule I, II, III, IV, V --> |
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| legal_US = <!-- OTC / Rx-only / Schedule I, II, III, IV, V --> |
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| legal_status = Legal |
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| legal_status = Legal |
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| routes_of_administration = |
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| routes_of_administration = |
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<!--Pharmacokinetic data--> |
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<!--Pharmacokinetic data--> |
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| metabolism = |
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| metabolism = |
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| elimination_half-life = |
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| elimination_half-life = |
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| excretion = |
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| excretion = |
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<!--Identifiers--> |
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<!--Identifiers--> |
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| CAS_number_Ref = {{cascite|correct|??}} |
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| CAS_number_Ref = {{cascite|changed|??}} |
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| CAS_number = <!-- blanked - oldvalue: 92623-83-1 --> |
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| CAS_number = 92623-83-1 |
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| ATC_prefix = none |
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| ATC_prefix = none |
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| ATC_suffix = |
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| ATC_suffix = |
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| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} |
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| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} |
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| ChemSpiderID = 50942 |
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| ChemSpiderID = 50942 |
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| UNII_Ref = {{fdacite|changed|FDA}} |
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| UNII_Ref = {{fdacite|correct|FDA}} |
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| UNII = P3JW662TWA |
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| UNII = P3JW662TWA |
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| ChEMBL_Ref = {{ebicite|correct|EBI}} |
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| ChEMBL_Ref = {{ebicite|correct|EBI}} |
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<!--Chemical data--> |
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<!--Chemical data--> |
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| C=23 | H=26 | N=2 | O=3 |
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| C=23 | H=26 | N=2 | O=3 |
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| molecular_weight = 378.46 g/mol |
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| smiles = O=C(c1ccc(OC)cc1)c2c4ccccc4n(c2C)CCN3CCOCC3 |
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| smiles = O=C(c1ccc(OC)cc1)c2c4ccccc4n(c2C)CCN3CCOCC3 |
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| InChI = 1/C23H26N2O3/c1-17-22(23(26)18-7-9-19(27-2)10-8-18)20-5-3-4-6-21(20)25(17)12-11-24-13-15-28-16-14-24/h3-10H,11-16H2,1-2H3 |
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| InChIKey = MEUQWHZOUDZXHH-UHFFFAOYAE |
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| StdInChI_Ref = {{stdinchicite|correct|chemspider}} |
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| StdInChI_Ref = {{stdinchicite|correct|chemspider}} |
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| StdInChI = 1S/C23H26N2O3/c1-17-22(23(26)18-7-9-19(27-2)10-8-18)20-5-3-4-6-21(20)25(17)12-11-24-13-15-28-16-14-24/h3-10H,11-16H2,1-2H3 |
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| StdInChI = 1S/C23H26N2O3/c1-17-22(23(26)18-7-9-19(27-2)10-8-18)20-5-3-4-6-21(20)25(17)12-11-24-13-15-28-16-14-24/h3-10H,11-16H2,1-2H3 |
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| StdInChIKey = MEUQWHZOUDZXHH-UHFFFAOYSA-N |
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| StdInChIKey = MEUQWHZOUDZXHH-UHFFFAOYSA-N |
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}} |
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}} |
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'''Pravadoline''' ('''WIN 48,098''') is an ] and ] drug with an ] of 4.9 μM and a ''K''<sub>i</sub> of 2511 nM at ], related in structure to ]s (NSAIDs) such as ]. It was developed in the 1980s as a new antiinflammatory and ] synthesis inhibitor, acting through inhibition of the enzyme ] (COX). |
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However, pravadoline was found to exhibit unexpectedly strong analgesic effects, which appeared at doses ten times smaller than the effective anti-inflammatory dose and so could not be explained by its action as a ]. These effects were not blocked by opioid ] such as ],<ref name="pmid2243340">{{cite journal |vauthors=Haubrich DR, etal |title=Pharmacology of pravadoline: a new analgesic agent |journal=J. Pharmacol. Exp. Ther. |volume=255 |issue=2 |pages=511–22 |year=1990 |pmid=2243340 |url=http://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=2243340 }}</ref> and it was eventually discovered that pravadoline represented the first compound from a novel class of ] ]s, the aminoalkylindoles.<ref name="pmid1900533">{{cite journal |vauthors=Bell MR, etal |title=Antinociceptive (aminoalkyl)indoles |journal=J. Med. Chem. |volume=34 |issue=3 |pages=1099–110 |year=1991 |pmid=1900533 |doi=10.1021/jm00107a034 }}</ref> |
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Pravadoline was never developed for use as an analgesic, partly due to toxicity concerns (although these were later shown to be a result of the salt form that the drug had been prepared in rather than from the pravadoline itself),<ref name="pmid8365586">{{cite journal |vauthors=Everett RM, etal |title=Nephrotoxicity of pravadoline maleate (WIN 48098-6) in dogs: evidence of maleic acid-induced acute tubular necrosis |journal=Fundam Appl Toxicol |volume=21 |issue=1 |pages=59–65 |year=1993 |pmid=8365586 |doi=10.1006/faat.1993.1072 |
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}}</ref> however the discovery of cannabinoid activity in this structurally novel family of drugs led to the discovery of several new cannabinoid agonists, including the drug ], which is now widely used in scientific research.<ref name="pmid1732519">{{cite journal |vauthors=D'Ambra TE, etal |title=Conformationally restrained analogues of pravadoline: nanomolar potent, enantioselective, (aminoalkyl)indole agonists of the cannabinoid receptor |journal=J. Med. Chem. |volume=35 |issue=1 |pages=124–35 |year=1992 |pmid=1732519 |doi=10.1021/jm00079a016 }}</ref><ref name="pmid1335057">{{cite journal |vauthors=Compton DR, etal |title=Aminoalkylindole analogs: cannabimimetic activity of a class of compounds structurally distinct from delta 9-tetrahydrocannabinol |journal=J. Pharmacol. Exp. Ther. |volume=263 |issue=3 |pages=1118–26 |year=1992 |pmid=1335057 |
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|url=http://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=1335057}}</ref> |
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==Animal studies== |
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Administration of pravadoline on rats showed:<ref name="pmid2243340" /> |
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* Prolonged the response latency induced by tail immersion in hot water at a temperature of 55 °C (minimum effective dose 100 mg/kg s.c.) |
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* Prevented ] in rats with ] injections during (]) (minimum effective dose 1 mg/kg, p.o.) |
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* Prevented the ] response induced by paw flexion in the ]-arthritic rat (ED<sub>50</sub> 41 mg/kg, p.o.) |
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* Prevented the nociceptive response of ]-induced head and forepaw flexion (ED<sub>50</sub> 78 mg/kg, p.o.) |
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The antinociceptive activity of pravadoline cannot be explained by an opioid mechanism, because pravadoline-induced antinociception was not antagonized by naloxone (1 mg/kg, s.c.) and pravadoline did not bind to the ]s at concentrations up to 10 μM.<ref name="pmid2243340" /> |
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==See also== |
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* ] (6-iodopravadoline) |
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* ] (6-bromopravadoline) |
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* ] |
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* ] (1-pentyl-3-(4-methoxybenzoyl)indole) |
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==References== |
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{{Reflist}} |
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{{Cannabinoids}} |
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{{Cannabinoid receptor modulators}} |
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] |
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] |
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] |
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] |
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] |