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Tacrine
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<h2 id="clinical-use">Clinical use</h2> <p>Tacrine was the prototypical <a href="/facts/Cholinesterase_inhibitor/dQ2jMc8H">cholinesterase inhibitor</a> for the treatment of <a href="/facts/Alzheimer%27s_disease/w7Ad6tdg">Alzheimer's disease</a>. <a href="/facts/William_K._Summers/LTqNEHbs">William K. Summers</a> received a patent for this use in 1989.<a class="footnote-ref" id="fnref:2" href="#fn:2"><sup>2</sup></a><a class="footnote-ref" id="fnref:3" href="#fn:3"><sup>3</sup></a><a class="footnote-ref" id="fnref:4" href="#fn:4"><sup>4</sup></a> Studies found that it may have a small beneficial effect on cognition and other clinical measures, though study data was limited and the clinical relevance of these findings was unclear.<a class="footnote-ref" id="fnref:5" href="#fn:5"><sup>5</sup></a><a class="footnote-ref" id="fnref:6" href="#fn:6"><sup>6</sup></a> </p><p>Tacrine has been discontinued in the <a href="/facts/United_States_of_America/P0sCdLe5">US</a><a class="footnote-ref" id="fnref:7" href="#fn:7"><sup>7</sup></a> in 2013, due to concerns over safety.<a class="footnote-ref" id="fnref:8" href="#fn:8"><sup>8</sup></a> </p><p>Tacrine was also described as an <a href="/facts/Analeptic/vPMdSJUe">analeptic</a> agent used to promote mental alertness.<a class="footnote-ref" id="fnref:9" href="#fn:9"><sup>9</sup></a> </p> <h2 id="adverse-effects">Adverse effects</h2> Very common (>10% incidence) adverse effects include<a class="footnote-ref" id="fnref:10" href="#fn:10"><sup>10</sup></a> <ul><li>Increased <a href="/facts/Liver_function_tests/IGuSa6Hn">liver function tests</a> (LFT), with 49% of patients displaying elevated <a href="/facts/Alanine_transaminase/PAUfv2UK">ALA</a><a class="footnote-ref" id="fnref:11" href="#fn:11"><sup>11</sup></a></li> <li>Diarrhea</li> <li>Dizziness</li> <li>Headache</li> <li>Nausea</li> <li>Vomiting</li></ul> Common (1-10% incidence) adverse effects include<a class="footnote-ref" id="fnref:12" href="#fn:12"><sup>12</sup></a><a class="footnote-ref" id="fnref:13" href="#fn:13"><sup>13</sup></a> <ul><li>Abdominal pain</li> <li>Agitation</li> <li>Anxiety</li> <li>Ataxia — decreased control over bodily movements.</li> <li>Belching</li> <li>Confusion</li> <li><a href="/facts/Conjunctivitis/u1NJfh3A">Conjunctivitis</a> (a link to tacrine treatment has not been conclusively proven)</li> <li>Constipation</li> <li>Diaphoresis — sweating.</li> <li>Fatigue</li> <li>Hallucinations</li> <li>Indigestion</li> <li>Insomnia</li> <li>Myalgia — muscle pain</li> <li>Rash</li> <li>Rhinitis</li> <li>Somnolence</li> <li>Tremor</li> <li>Urinary incontinence</li> <li>Weight loss</li></ul> Uncommon/rare (<1% incidence) adverse effects include<a class="footnote-ref" id="fnref:14" href="#fn:14"><sup>14</sup></a> <ul><li><a href="/facts/Agranulocytosis/3AP5MDpD">Agranulocytosis</a> (a link between treatment and this adverse effect has not been proven) — a potentially fatal drop in white blood cells, the body's immune/defensive cells.</li> <li>Hepatotoxicity (<i>that is</i> toxic effects on the liver)</li> <li>Ototoxicity (hearing/ear damage; a link to tacrine treatment has not been conclusively proven)</li> <li>Seizures</li> <li>Taste changes</li></ul> Unknown incidence adverse effects include<a class="footnote-ref" id="fnref:15" href="#fn:15"><sup>15</sup></a> <ul><li><a href="/facts/Bradycardia/70msP5HD">Bradycardia</a></li> <li>Delirium</li> <li>Depression</li> <li>Hypotension</li> <li>Suicidal ideation and behaviour</li> <li><a href="/facts/Urinary_tract_infection/4NwY9tL0">Urinary tract infection</a></li> <li>Other optic effects such as <a href="/facts/Glaucoma/MWqWVNz3">glaucoma</a>, <a href="/facts/Cataracts/RzN7k7K2">cataracts</a>, etc. (also not conclusively linked to tacrine treatment)</li></ul> <h3>Overdose</h3> <p>As stated above, overdosage of tacrine may give rise to severe side effects such as nausea, vomiting, salivation, sweating, bradycardia, hypotension, collapse, and convulsions. <a href="/facts/Atropine/cJQ0gL4o">Atropine</a> is a popular treatment for overdose.<a class="footnote-ref" id="fnref:16" href="#fn:16"><sup>16</sup></a> </p> <h2 id="pharmacokinetics">Pharmacokinetics</h2> <p>Major form of metabolism is in the liver via hydroxylation of benzylic carbon by <a href="/facts/CYP1A2/U69VPyRC">CYP1A2</a>. This forms the major metabolite 1-hydroxy-tacrine (velnacrine) which is still active.<a class="footnote-ref" id="fnref:17" href="#fn:17"><sup>17</sup></a> </p> <h2 id="external-links">External links</h2> <ul><li><a href="http://www.ebi.ac.uk/pdbe/quips?story=AChE">Acetylcholinesterase: A gorge-ous enzyme</a> QUite Interesting PDB Structure article at <a href="http://www.pdbe.org">PDBe</a></li></ul> <h2 id="references">References</h2> <ol> <li id="fn:1"><p>Taraschenko OD, Barnes WG, Herrick-Davis K, Yokoyama Y, Boyd DL, Hough LB (April 2005). "Actions of tacrine and galanthamine on histamine-N-methyltransferase". Methods and Findings in Experimental and Clinical Pharmacology. 27 (3): 161–165. doi:10.1358/mf.2005.27.3.890872. PMID 15834447. <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:1" class="footnote-back-ref">↩</a></p></li> <li id="fn:2"><p>US 4816456, Summers WK, "Administration of monoamine acridines in cholinergic neuronal deficit states", issued 28 March 1989 <a href="https://worldwide.espacenet.com/textdoc?DB=EPODOC&IDX=US4816456" target="_blank">https://worldwide.espacenet.com/textdoc?DB=EPODOC&IDX=US4816456</a> <a href="#fnref:2" class="footnote-back-ref">↩</a></p></li> <li id="fn:3"><p>Waldholz M (4 August 1987). A Psychiatrist's work leads to a US study of Alzheimer's drug: but Dr. Summers shuns test, seeks to widen his own; is Memory really aided; Fee-for research Furor. Wall Street Journal (Report). p. A-1. <a href="#fnref:3" class="footnote-back-ref">↩</a></p></li> <li id="fn:4"><p>Peacock D (25 March 2005). "New Mexico Doctor invents drugs, supplements for Alzheimer's disease, Multiple Sclerosis". NM Bus Weekly. <a href="https://www.bizjournals.com/albuquerque/stories/2005/03/28/smallb2.html" target="_blank">https://www.bizjournals.com/albuquerque/stories/2005/03/28/smallb2.html</a> <a href="#fnref:4" class="footnote-back-ref">↩</a></p></li> <li id="fn:5"><p>Qizilbash N, Whitehead A, Higgins J, Wilcock G, Schneider L, Farlow M (November 1998). "Cholinesterase inhibition for Alzheimer disease: a meta-analysis of the tacrine trials. Dementia Trialists' Collaboration". JAMA. 280 (20): 1777–1782. doi:10.1001/jama.280.20.1777. PMID 9842955. <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:5" class="footnote-back-ref">↩</a></p></li> <li id="fn:6"><p>Rang HP, Dale MM, Ritter JM, Moore PK (2003). Pharmacology (5th ed.). Edinburgh: Churchill Livingstone. ISBN 978-0-443-07145-4.. <a href="978-0-443-07145-4" target="_blank">978-0-443-07145-4</a> <a href="#fnref:6" class="footnote-back-ref">↩</a></p></li> <li id="fn:7"><p>"tacrine (Discontinued) - Cognex". Medscape Reference. WebMD. Archived from the original on 30 June 2019. Retrieved 8 October 2013. <a href="https://web.archive.org/web/20190630162718/https://reference.medscape.com/drug/tacrine-343070" target="_blank">https://web.archive.org/web/20190630162718/https://reference.medscape.com/drug/tacrine-343070</a> <a href="#fnref:7" class="footnote-back-ref">↩</a></p></li> <li id="fn:8"><p>"Tacrine". LiverTox. U.S. National Institutes of Health. Archived from the original on 2019-07-02. <a href="https://web.archive.org/web/20190702153735/http://www.livertox.nih.gov/Tacrine.htm" target="_blank">https://web.archive.org/web/20190702153735/http://www.livertox.nih.gov/Tacrine.htm</a> <a href="#fnref:8" class="footnote-back-ref">↩</a></p></li> <li id="fn:9"><p>Elks J, Ganellin CR, eds. (1990). Dictionary of Drugs. doi:10.1007/978-1-4757-2085-3. ISBN 978-1-4757-2087-7. <a href="978-1-4757-2087-7" target="_blank">978-1-4757-2087-7</a> <a href="#fnref:9" class="footnote-back-ref">↩</a></p></li> <li id="fn:10"><p>"tacrine (Discontinued) - Cognex". Medscape Reference. WebMD. Archived from the original on 30 June 2019. Retrieved 8 October 2013. <a href="https://web.archive.org/web/20190630162718/https://reference.medscape.com/drug/tacrine-343070" target="_blank">https://web.archive.org/web/20190630162718/https://reference.medscape.com/drug/tacrine-343070</a> <a href="#fnref:10" class="footnote-back-ref">↩</a></p></li> <li id="fn:11"><p>Watkins PB, Zimmerman HJ, Knapp MJ, Gracon SI, Lewis KW (April 1994). "Hepatotoxic effects of tacrine administration in patients with Alzheimer's disease". JAMA. 271 (13): 992–998. doi:10.1001/jama.1994.03510370044030. PMID 8139084. <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:11" class="footnote-back-ref">↩</a></p></li> <li id="fn:12"><p>"tacrine (Discontinued) - Cognex". Medscape Reference. WebMD. Archived from the original on 30 June 2019. Retrieved 8 October 2013. <a href="https://web.archive.org/web/20190630162718/https://reference.medscape.com/drug/tacrine-343070" target="_blank">https://web.archive.org/web/20190630162718/https://reference.medscape.com/drug/tacrine-343070</a> <a href="#fnref:12" class="footnote-back-ref">↩</a></p></li> <li id="fn:13"><p>Truven Health Analytics, Inc. DRUGDEX® System (Internet) [cited 2013 Oct 8]. Greenwood Village, CO: Thomsen Healthcare; 2013. <a href="#fnref:13" class="footnote-back-ref">↩</a></p></li> <li id="fn:14"><p>Truven Health Analytics, Inc. DRUGDEX® System (Internet) [cited 2013 Oct 8]. Greenwood Village, CO: Thomsen Healthcare; 2013. <a href="#fnref:14" class="footnote-back-ref">↩</a></p></li> <li id="fn:15"><p>Truven Health Analytics, Inc. DRUGDEX® System (Internet) [cited 2013 Oct 8]. Greenwood Village, CO: Thomsen Healthcare; 2013. <a href="#fnref:15" class="footnote-back-ref">↩</a></p></li> <li id="fn:16"><p>Truven Health Analytics, Inc. DRUGDEX® System (Internet) [cited 2013 Oct 8]. Greenwood Village, CO: Thomsen Healthcare; 2013. <a href="#fnref:16" class="footnote-back-ref">↩</a></p></li> <li id="fn:17"><p>Truven Health Analytics, Inc. DRUGDEX® System (Internet) [cited 2013 Oct 8]. Greenwood Village, CO: Thomsen Healthcare; 2013. <a href="#fnref:17" class="footnote-back-ref">↩</a></p></li> </ol>