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Memantine
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<h2 id="medical-uses">Medical uses</h2> <h3>Alzheimer's disease and dementia</h3> <p>Memantine is used to treat moderate-to-severe Alzheimer's disease, especially for people who are intolerant of or have a contraindication to <a href="/facts/Acetylcholinesterase/9pLwD1b9">AChE (acetylcholinesterase)</a> <a href="/facts/Acetylcholinesterase_inhibitor/VbN36u7y">inhibitors</a>.<a class="footnote-ref" id="fnref:20" href="#fn:20"><sup>20</sup></a><a class="footnote-ref" id="fnref:21" href="#fn:21"><sup>21</sup></a> One guideline recommends memantine or an AChE inhibitor be considered in people in the early-to-mid stage of dementia.<a class="footnote-ref" id="fnref:22" href="#fn:22"><sup>22</sup></a> </p><p>Memantine has been associated with a modest improvement;<a class="footnote-ref" id="fnref:23" href="#fn:23"><sup>23</sup></a> with small positive effects on <a href="/facts/Cognition/ga0tSBul">cognition</a>, mood, behavior, and the ability to perform daily activities in moderate-to-severe Alzheimer's disease.<a class="footnote-ref" id="fnref:24" href="#fn:24"><sup>24</sup></a><a class="footnote-ref" id="fnref:25" href="#fn:25"><sup>25</sup></a> There does not appear to be any benefit in mild disease.<a class="footnote-ref" id="fnref:26" href="#fn:26"><sup>26</sup></a> </p><p>Memantine when added to <a href="/facts/Donepezil/kmCkGdVx">donepezil</a> in those with moderate-to-severe dementia resulted in "limited improvements" in a 2017 review.<a class="footnote-ref" id="fnref:27" href="#fn:27"><sup>27</sup></a> The UK <a href="/facts/National_Institute_for_Clinical_Excellence/83vtP8Lk">National Institute for Clinical Excellence</a> (NICE) issued guidance in 2018 recommending consideration of the combination of memantine with donepezil in those with moderate-to-severe dementia.<a class="footnote-ref" id="fnref:28" href="#fn:28"><sup>28</sup></a> </p> <h3>Radiation therapy</h3> <p>Memantine has been recommended for use by professional organization consensus to prevent neurocognitive decline after <a href="/facts/Whole_brain_radiotherapy/AKBaDmV7">whole brain radiotherapy</a>.<a class="footnote-ref" id="fnref:29" href="#fn:29"><sup>29</sup></a> </p> <h2 id="adverse-effects">Adverse effects</h2> <p>Memantine is, in general, well tolerated.<a class="footnote-ref" id="fnref:30" href="#fn:30"><sup>30</sup></a> Common <a href="/facts/Adverse_drug_reaction/Ea0ktF6J">adverse drug reactions</a> (≥1% of people) include confusion, dizziness, drowsiness, headache, insomnia, agitation, and/or hallucinations. Less common adverse effects include <a href="/facts/Vomiting/R2vQkHqV">vomiting</a>, anxiety, <a href="/facts/Hypertonia/VfDaQvgj">hypertonia</a>, <a href="/facts/Cystitis/4NwY9tL0">cystitis</a>, and increased <a href="/facts/Libido/g1Eb72tA">libido</a>.<a class="footnote-ref" id="fnref:31" href="#fn:31"><sup>31</sup></a><a class="footnote-ref" id="fnref:32" href="#fn:32"><sup>32</sup></a> </p><p>Like many other <a href="/facts/NMDA_receptor_antagonist/4VJvEpdK">NMDA receptor antagonists</a>, memantine behaves as a <a href="/facts/Dissociative_anesthetic/5aaD39vM">dissociative anesthetic</a> at supratherapeutic doses.<a class="footnote-ref" id="fnref:33" href="#fn:33"><sup>33</sup></a> Despite isolated reports, <a href="/facts/Recreational_drug_use/eoBD3vKn">recreational use</a> of memantine is rare due to the drug's long duration and limited availability.<a class="footnote-ref" id="fnref:34" href="#fn:34"><sup>34</sup></a> Additionally, memantine seems to lack effects such as <a href="/facts/Euphoria/u4cnbWC4">euphoria</a> or <a href="/facts/Hallucination/5eUvLcnp">hallucinations</a>.<a class="footnote-ref" id="fnref:35" href="#fn:35"><sup>35</sup></a> </p><p>Memantine appears to be generally well tolerated by children with <a href="/facts/Autism_spectrum_disorder/bzouRyMI">autism spectrum disorder</a>.<a class="footnote-ref" id="fnref:36" href="#fn:36"><sup>36</sup></a> </p> <h2 id="pharmacology">Pharmacology</h2> <h3>Pharmacodynamics</h3> <h4>Glutamatergic</h4> <p>A dysfunction of <a href="/facts/Glutamatergic/IQJ5kJjG">glutamatergic</a> <a href="/facts/Neurotransmission/9H38LExu">neurotransmission</a>, manifested as <a href="/facts/Neuron/G7CyTVdH">neuronal</a> <a href="/facts/Excitotoxicity/DKnHA79x">excitotoxicity</a>, is hypothesized to be involved in the <a href="/facts/Etiology/Bz8MAeSq">etiology</a> of <a href="/facts/Alzheimer%2527s_disease/w7Ad6tdg">Alzheimer's disease</a>. Targeting the glutamatergic system, specifically <a href="/facts/Ionotropic_glutamate_receptor/RqSxqHqF">ionotropic glutamate</a> <a href="/facts/NMDA_receptor/BqMhXEbU">NMDA receptors</a>, offers a novel approach to treatment in view of the limited efficacy of existing drugs targeting the <a href="/facts/Cholinergic/51ttI8RK">cholinergic</a> system.<a class="footnote-ref" id="fnref:37" href="#fn:37"><sup>37</sup></a> </p><p>Memantine is a low-affinity voltage-dependent <a href="/facts/Uncompetitive_inhibitor/nPvDGaAc">uncompetitive</a> <a href="/facts/NMDA_receptor_antagonist/4VJvEpdK">antagonist at glutamatergic NMDA receptors</a>.<a class="footnote-ref" id="fnref:38" href="#fn:38"><sup>38</sup></a><a class="footnote-ref" id="fnref:39" href="#fn:39"><sup>39</sup></a> By binding to the NMDA receptor with a higher affinity than <a href="/facts/Magnesium/XyIhd2FG">Mg2+</a> ions, memantine is able to inhibit the prolonged influx of <a href="/facts/Calcium/hf252CC0">Ca2+</a> ions, particularly from extrasynaptic receptors, which forms the basis of neuronal <a href="/facts/Excitotoxicity/DKnHA79x">excitotoxicity</a>. The low affinity, uncompetitive nature, and rapid off-rate kinetics of memantine at the level of the NMDA receptor channel, however, preserves the function of the receptor at synapses, as it can still be activated by physiological release of <a href="/facts/Glutamate/7oXbNcvu">glutamate</a> following <a href="/facts/Depolarization/qGX8lFXE">depolarization</a> of the <a href="/facts/Postsynaptic/M1x5rhz7">postsynaptic</a> neuron.<a class="footnote-ref" id="fnref:40" href="#fn:40"><sup>40</sup></a><a class="footnote-ref" id="fnref:41" href="#fn:41"><sup>41</sup></a><a class="footnote-ref" id="fnref:42" href="#fn:42"><sup>42</sup></a> The interaction of memantine with NMDA receptors plays a major role in the symptomatic improvement that the drug produces in Alzheimer's disease. However, there is no evidence as yet that the ability of memantine to protect against extrasynaptic NMDA receptor-mediated excitotoxicity has a disease-modifying effect in Alzheimer's disease, although this has been suggested in animal models.<a class="footnote-ref" id="fnref:43" href="#fn:43"><sup>43</sup></a> </p> <h4>Serotonergic</h4> <p>Memantine acts as a <a href="/facts/Non-competitive_antagonist/PuXHVNdV">non-competitive antagonist</a> of the <a href="/facts/Serotonin/EzY58q4a">serotonin</a> <a href="/facts/5-HT3_receptor/7Qa2T8v3">5-HT3 receptor</a>, with a <a href="/facts/Potency_(pharmacology)/D38FDyPh">potency</a> similar to that for the NMDA receptor.<a class="footnote-ref" id="fnref:44" href="#fn:44"><sup>44</sup></a> Many 5-HT3 receptor antagonists function as <a href="/facts/Antiemetic/GEqXzKJJ">antiemetics</a>, however the clinical significance of this <a href="/facts/Serotonin_antagonist/Fp9DX8oW">anti-serotonergic</a> activity of memantine in Alzheimer's disease is unknown. </p> <h4>Cholinergic</h4> <p>Memantine acts as a <a href="/facts/Non-competitive_antagonist/PuXHVNdV">non-competitive antagonist</a> of different neuronal <a href="/facts/Nicotinic_acetylcholine_receptor/k2s2pPHr">nicotinic acetylcholine receptors</a> (nAChRs) at potencies possibly similar to the NMDA receptor and 5-HT3 receptor, but this is difficult to ascertain with accuracy because of the rapid desensitization of nAChR responses in these experiments. It can be noted that memantine is an antagonist at <a href="/facts/Alpha-7_nicotinic_receptor/Q4hcBmDE">α7 nAChR</a>, which may contribute to initial worsening of cognitive function during early memantine treatment. α7 nAChR <a href="/facts/Downregulation_and_upregulation/6nRoa28r">upregulates</a> quickly in response to antagonism, which could explain the cognitive-enhancing effects of chronic memantine treatment.<a class="footnote-ref" id="fnref:45" href="#fn:45"><sup>45</sup></a><a class="footnote-ref" id="fnref:46" href="#fn:46"><sup>46</sup></a> It has been shown that the number of <a href="/facts/Nicotinic_receptor/k2s2pPHr">nicotinic receptors</a> in the brain are reduced in Alzheimer's disease, even in the absence of a general decrease in the number of neurons, and <a href="/facts/Nicotinic_receptor/k2s2pPHr">nicotinic receptor</a> <a href="/facts/Agonists/nz8U5NNp">agonists</a> are viewed as interesting targets for anti-Alzheimer drugs.<a class="footnote-ref" id="fnref:47" href="#fn:47"><sup>47</sup></a> </p> <h4>Dopaminergic</h4> <p>Memantine was shown in a study to act as an agonist at the <a href="/facts/Dopamine/5gNy8Xkd">dopamine</a> <a href="/facts/D2_receptor/SmmP3QyU">D2high receptor</a> with equal or slightly higher affinity than to the NMDA receptors.<a class="footnote-ref" id="fnref:48" href="#fn:48"><sup>48</sup></a> However, the relevance of this action may be negligible, as studies have shown very low affinity for binding to D2 receptors in general.<a class="footnote-ref" id="fnref:49" href="#fn:49"><sup>49</sup></a> </p> <h4>Sigmaergic</h4> <p>Memantine acts as an <a href="/facts/Agonist/nz8U5NNp">agonist</a> of the <a href="/facts/Sigma_receptor/JpFeF344">sigma</a> <a href="/facts/Sigma-1_receptor/qje6l9GW">σ1 receptor</a> with low <a href="/facts/Affinity_(pharmacology)/44QLL4eU">affinity</a> (Ki = 2.6 μM).<a class="footnote-ref" id="fnref:50" href="#fn:50"><sup>50</sup></a> The consequences of this activity are unclear (as the role of sigma receptors in general is currently not very well understood). Due to this low affinity, therapeutic concentrations of memantine are most likely too low to have any sigmaergic effect as a typical therapeutic dose is 20 mg. However, excessive doses of memantine taken for recreational purposes many times greater than prescribed doses may indeed activate this receptor.<a class="footnote-ref" id="fnref:51" href="#fn:51"><sup>51</sup></a> </p> <h4>Other actions</h4> <p>Memantine does not appear to <a href="/facts/Enzyme_inhibitor/MkFwGXHJ">inhibit</a> or <a href="/facts/Enzyme_inducer/k3S7bhdA">induce</a> several <a href="/facts/Cytochrome_P450/alxusFD0">cytochrome P450</a> <a href="/facts/Enzyme/DSI1Fh7y">enzymes</a> including <a href="/facts/CYP3A4/MqD09gEj">CYP3A4</a>/<a href="/facts/CYP3A5/UEBUlHPr">5</a>, <a href="/facts/CYP1A2/U69VPyRC">CYP1A2</a>, <a href="/facts/CYP2D6/Gx1MovPA">CYP2D6</a>, and <a href="/facts/CYP2C9/X5K24aNl">CYP2C9</a>.<a class="footnote-ref" id="fnref:52" href="#fn:52"><sup>52</sup></a> It also does not inhibit <a href="/facts/CYP2A6/rcK5p3HT">CYP2A6</a> or <a href="/facts/CYP2E1/T8RrnGdW">CYP2E1</a>.<a class="footnote-ref" id="fnref:53" href="#fn:53"><sup>53</sup></a> However, it might have a small effect on <a href="/facts/CYP2B6/gkM9tRSJ">CYP2B6</a>.<a class="footnote-ref" id="fnref:54" href="#fn:54"><sup>54</sup></a> </p> <h3>Pharmacokinetics</h3> <h4>Absorption</h4> <p>The <a href="/facts/Oral_administration/vNQcvLVx">oral</a> <a href="/facts/Bioavailability/9l6na9MV">bioavailability</a> of memantine is 100%.<a class="footnote-ref" id="fnref:55" href="#fn:55"><sup>55</sup></a><a class="footnote-ref" id="fnref:56" href="#fn:56"><sup>56</sup></a> <a href="/facts/Tmax_(pharmacology)/IceQcRQB">Time to peak</a> levels of memantine is 3 to 7 hours.<a class="footnote-ref" id="fnref:57" href="#fn:57"><sup>57</sup></a><a class="footnote-ref" id="fnref:58" href="#fn:58"><sup>58</sup></a> <a href="/facts/Food/RgNq6NAK">Food</a> has no influence on the rate of <a href="/facts/Absorption_(pharmacokinetics)/LCezQPJK">absorption</a>.<a class="footnote-ref" id="fnref:59" href="#fn:59"><sup>59</sup></a><a class="footnote-ref" id="fnref:60" href="#fn:60"><sup>60</sup></a> Memantine exposure is linear over a dose range of 10 to 40 mg.<a class="footnote-ref" id="fnref:61" href="#fn:61"><sup>61</sup></a> <a href="/facts/Cmax_(pharmacology)/IceQcRQB">Peak</a> levels after a single 20 mg dose were found to be 24 to 29 μg/L (0.13–0.16 μmol/L or μM).<a class="footnote-ref" id="fnref:62" href="#fn:62"><sup>62</sup></a> <a href="/facts/Steady-state_levels/x4CUUnle">Steady-state levels</a> of memantine with 20 mg/day are in the range of 0.5 to 1.0 μM.<a class="footnote-ref" id="fnref:63" href="#fn:63"><sup>63</sup></a> </p> <h4>Distribution</h4> <p>Memantine has a relatively high <a href="/facts/Volume_of_distribution/64B8XegG">volume of distribution</a> (Vd) of 9 to 11 L/kg.<a class="footnote-ref" id="fnref:64" href="#fn:64"><sup>64</sup></a><a class="footnote-ref" id="fnref:65" href="#fn:65"><sup>65</sup></a> It easily crosses <a href="/facts/Biological_membrane/ljBsfK4r">biological membranes</a>, is widely <a href="/facts/Distribution_(pharmacology)/f8Hkox6Q">distributed</a> throughout the body, and crosses the <a href="/facts/Blood%25E2%2580%2593brain_barrier/xYzvVwdu">blood–brain barrier</a> into the <a href="/facts/Central_nervous_system/k8I6To97">central nervous system</a>.<a class="footnote-ref" id="fnref:66" href="#fn:66"><sup>66</sup></a> The drug is <a href="/facts/Membrane_transport/0wgnDr2c">transported</a> across the blood–brain barrier by the <a href="/facts/OCTN1/jhnDuT65">organic cation transporter novel 1</a> (OCTN1).<a class="footnote-ref" id="fnref:67" href="#fn:67"><sup>67</sup></a> The <a href="/facts/Plasma_protein_binding/7u7qFYmb">plasma protein binding</a> of memantine is 45% and is described as very low and not clinically significant.<a class="footnote-ref" id="fnref:68" href="#fn:68"><sup>68</sup></a><a class="footnote-ref" id="fnref:69" href="#fn:69"><sup>69</sup></a> Because of its low plasma protein binding, it is unlikely to interact with other highly protein-bound drugs such as <a href="/facts/Warfarin/kMnH6tb0">warfarin</a> or <a href="/facts/Digoxin/JEHbskXq">digoxin</a>.<a class="footnote-ref" id="fnref:70" href="#fn:70"><sup>70</sup></a> </p> <h4>Metabolism</h4> <p>Memantine does not undergo extensive <a href="/facts/Drug_metabolism/I5nQ28Ma">metabolism</a>.<a class="footnote-ref" id="fnref:71" href="#fn:71"><sup>71</sup></a> It is negligibly <a href="/facts/Drug_metabolism/I5nQ28Ma">metabolized</a> by the <a href="/facts/Cytochrome_P450/alxusFD0">cytochrome P450</a> <a href="/facts/Enzyme/DSI1Fh7y">enzymes</a>.<a class="footnote-ref" id="fnref:72" href="#fn:72"><sup>72</sup></a><a class="footnote-ref" id="fnref:73" href="#fn:73"><sup>73</sup></a> As a result, it has a decreased potential for <a href="/facts/Drug_interaction/T5VcSVGd">drug interactions</a>.<a class="footnote-ref" id="fnref:74" href="#fn:74"><sup>74</sup></a> <a href="/facts/Metabolite/nAyywVtA">Metabolites</a> of memantine include memantine glucuronide, 6-hydroxymemantine, and 1-nitrosomemantine, all of which show minimal activity as NMDA receptor antagonists.<a class="footnote-ref" id="fnref:75" href="#fn:75"><sup>75</sup></a><a class="footnote-ref" id="fnref:76" href="#fn:76"><sup>76</sup></a> </p> <h4>Elimination</h4> <p>Memantine is <a href="/facts/Elimination_(pharmacology)/E0LubyYL">eliminated</a> primarily in <a href="/facts/Urine/oNUYVtvX">urine</a>, with 57 to 82% <a href="/facts/Excretion/mspsTfnv">excreted</a> in urine unchanged.<a class="footnote-ref" id="fnref:77" href="#fn:77"><sup>77</sup></a><a class="footnote-ref" id="fnref:78" href="#fn:78"><sup>78</sup></a> Its <a href="/facts/Elimination_half-life/7nB2JtMr">elimination half-life</a> is 60 to 80 hours.<a class="footnote-ref" id="fnref:79" href="#fn:79"><sup>79</sup></a><a class="footnote-ref" id="fnref:80" href="#fn:80"><sup>80</sup></a> The <a href="/facts/Kidney/HBspPrv9">renal</a> <a href="/facts/Clearance_(pharmacology)/RqI64paT">clearance</a> of memantine is dependent on <a href="/facts/Urine/oNUYVtvX">urinary</a> <a href="/facts/PH/RnSv8D7y">pH</a>.<a class="footnote-ref" id="fnref:81" href="#fn:81"><sup>81</sup></a><a class="footnote-ref" id="fnref:82" href="#fn:82"><sup>82</sup></a> More <a href="/facts/Alkaline/s6NqPGSP">alkaline</a> urine slows the elimination of memantine, whereas more <a href="/facts/Acid/FySU18n1">acidic</a> urine accelerates its elimination.<a class="footnote-ref" id="fnref:83" href="#fn:83"><sup>83</sup></a><a class="footnote-ref" id="fnref:84" href="#fn:84"><sup>84</sup></a> </p> <h2 id="chemistry">Chemistry</h2> <p>Memantine, also known as 3,5-dimethyl-1-aminoadamantane (DMAA), is an <a href="/facts/Adamantane/tlvgCxYf">adamantane</a> <a href="/facts/Chemical_derivative/JYcbLkbm">derivative</a> and is closely <a href="/facts/Structural_analog/3aysWSVG">structurally related</a> to <a href="/facts/Amantadine/wPfBx4Q4">amantadine</a> (1-aminoadamantane) and other adamantane derivatives.<a class="footnote-ref" id="fnref:85" href="#fn:85"><sup>85</sup></a><a class="footnote-ref" id="fnref:86" href="#fn:86"><sup>86</sup></a><a class="footnote-ref" id="fnref:87" href="#fn:87"><sup>87</sup></a><a class="footnote-ref" id="fnref:88" href="#fn:88"><sup>88</sup></a> </p><p>The <a href="/facts/Chemical_synthesis/3KXsVVwC">synthesis</a> of memantine has been described.<a class="footnote-ref" id="fnref:89" href="#fn:89"><sup>89</sup></a> </p> <h2 id="history">History</h2> <p class="note">Main article: <a href="/facts/Discovery_and_development_of_memantine_and_related_compounds/BqMhXEbU">Discovery and development of memantine and related compounds</a></p> <p>Memantine was first <a href="/facts/Chemical_synthesis/3KXsVVwC">synthesized</a>, <a href="/facts/Patent/LjT2bG3A">patented</a>, and described by <a href="/facts/Eli_Lilly_and_Company/e5Pw7RmR">Eli Lilly and Company</a> in 1963 as an <a href="/facts/Diabetes_medication/KIRV1BHj">anti-diabetic agent</a>, but it was ineffective at lowering <a href="/facts/Blood_sugar/I4SkNzrm">blood sugar</a>.<a class="footnote-ref" id="fnref:90" href="#fn:90"><sup>90</sup></a><a class="footnote-ref" id="fnref:91" href="#fn:91"><sup>91</sup></a><a class="footnote-ref" id="fnref:92" href="#fn:92"><sup>92</sup></a><a class="footnote-ref" id="fnref:93" href="#fn:93"><sup>93</sup></a><a class="footnote-ref" id="fnref:94" href="#fn:94"><sup>94</sup></a> By 1972, it was discovered to have <a href="/facts/Central_nervous_system/k8I6To97">central nervous system</a> (CNS) activity, and was developed by <a href="/facts/Merz_Pharma/BhfftMuD">Merz</a> for treatment of <a href="/facts/Neurological_disease/eQKKs7jX">neurological diseases</a>, such as <a href="/facts/Parkinson%2527s_disease/xpekKj6x">Parkinson's disease</a>.<a class="footnote-ref" id="fnref:95" href="#fn:95"><sup>95</sup></a><a class="footnote-ref" id="fnref:96" href="#fn:96"><sup>96</sup></a> Memantine was first studied in the treatment of <a href="/facts/Alzheimer%2527s_disease/w7Ad6tdg">Alzheimer's disease</a> in 1986.<a class="footnote-ref" id="fnref:97" href="#fn:97"><sup>97</sup></a><a class="footnote-ref" id="fnref:98" href="#fn:98"><sup>98</sup></a> The drug was first marketed for dementia in 1989 in Germany under the name Axura.<a class="footnote-ref" id="fnref:99" href="#fn:99"><sup>99</sup></a><a class="footnote-ref" id="fnref:100" href="#fn:100"><sup>100</sup></a><a class="footnote-ref" id="fnref:101" href="#fn:101"><sup>101</sup></a> </p><p>It was not discovered to act as an <a href="/facts/NMDA_receptor_antagonist/4VJvEpdK">NMDA receptor antagonist</a> until 1989, after clinical trials had initiated.<a class="footnote-ref" id="fnref:102" href="#fn:102"><sup>102</sup></a><a class="footnote-ref" id="fnref:103" href="#fn:103"><sup>103</sup></a><a class="footnote-ref" id="fnref:104" href="#fn:104"><sup>104</sup></a> Prior to this, it was theorized to directly and/or indirectly modulate the <a href="/facts/Dopaminergic/y2PcAHB2">dopaminergic</a>, <a href="/facts/Noradrenergic/AjTIC9ox">noradrenergic</a>, and <a href="/facts/Serotonergic_drug/EzY58q4a">serotonergic</a> systems.<a class="footnote-ref" id="fnref:105" href="#fn:105"><sup>105</sup></a><a class="footnote-ref" id="fnref:106" href="#fn:106"><sup>106</sup></a><a class="footnote-ref" id="fnref:107" href="#fn:107"><sup>107</sup></a><a class="footnote-ref" id="fnref:108" href="#fn:108"><sup>108</sup></a> However, these actions were later realized to occur at 100-fold higher concentrations than those achieved therapeutically and hence are unlikely to be involved in its effects.<a class="footnote-ref" id="fnref:109" href="#fn:109"><sup>109</sup></a><a class="footnote-ref" id="fnref:110" href="#fn:110"><sup>110</sup></a><a class="footnote-ref" id="fnref:111" href="#fn:111"><sup>111</sup></a> </p><p>In the United States, some CNS activities were discovered at <a href="/facts/Children%2527s_Hospital_of_Boston/zNzbMlHg">Children's Hospital of Boston</a> in 1990, and Children's licensed patents covering uses of memantine outside the field of ophthalmology to <a href="/facts/Neurobiological_Technologies/vy9ulA6v">Neurobiological Technologies</a> (NTI) in 1995.<a class="footnote-ref" id="fnref:112" href="#fn:112"><sup>112</sup></a> In 1998, NTI amended its agreement with Children's to allow Merz to take over development.<a class="footnote-ref" id="fnref:113" href="#fn:113"><sup>113</sup></a> </p><p>In 2000, Merz partnered with <a href="/facts/Forest_Laboratories/1WQ4JCeV">Forest</a> to develop the drug for Alzheimer's disease in the United States under the brand name Namenda.<a class="footnote-ref" id="fnref:114" href="#fn:114"><sup>114</sup></a><a class="footnote-ref" id="fnref:115" href="#fn:115"><sup>115</sup></a> In 2000, Merz partnered with Suntory for the Japanese market and with Lundbeck for other markets including Europe;<a class="footnote-ref" id="fnref:116" href="#fn:116"><sup>116</sup></a> the drug was originally marketed by Lundbeck under the name Ebixa.<a class="footnote-ref" id="fnref:117" href="#fn:117"><sup>117</sup></a> Memantine was approved in the <a href="/facts/European_Union/6GYcR8qM">European Union</a> in 2002 and in the United States in 2003.<a class="footnote-ref" id="fnref:118" href="#fn:118"><sup>118</sup></a><a class="footnote-ref" id="fnref:119" href="#fn:119"><sup>119</sup></a> </p><p>Sales of the drug reached $1.8 billion for 2014.<a class="footnote-ref" id="fnref:120" href="#fn:120"><sup>120</sup></a><a class="footnote-ref" id="fnref:121" href="#fn:121"><sup>121</sup></a> The cost of Namenda was $269 to $489 a month in 2012.<a class="footnote-ref" id="fnref:122" href="#fn:122"><sup>122</sup></a> </p><p>In February 2014, as the July 2015 patent expiration for memantine neared, <a href="/facts/Actavis/dJGoWIU3">Actavis</a>, which had acquired Forest, announced that it was launching an extended release (XR) form of memantine that could be taken once a day instead of twice a day as needed with the then-current "immediate release" (IR) version, and that it intended to stop selling the IR version in August 2014 and withdraw the marketing authorization. This is a tactic to thwart generic competition called <a href="/facts/Product_hopping/x1bEl18m">product hopping</a>. However the supply of the XR version ran short, so Actavis extended the deadline until the fall. In September 2014 the attorney general of New York, <a href="/facts/Eric_Schneiderman/CIBQoUn3">Eric Schneiderman</a>, filed a lawsuit to compel Actavis to keep selling the IR version on the basis of <a href="/facts/United_States_antitrust_law/Gr2aLDGj">antitrust law</a>.<a class="footnote-ref" id="fnref:123" href="#fn:123"><sup>123</sup></a><a class="footnote-ref" id="fnref:124" href="#fn:124"><sup>124</sup></a> </p><p>In December 2014, a judge granted New York State its request and issued an injunction, preventing Actavis from withdrawing the IR version until generic versions could launch. Actavis appealed and in May a panel of the <a href="/facts/Second_Circuit_Court_of_Appeals/wgLacmcA">Second Circuit Court of Appeals</a> upheld the injunction, and in June Actavis asked that its case be heard by the full Second Circuit panel.<a class="footnote-ref" id="fnref:125" href="#fn:125"><sup>125</sup></a><a class="footnote-ref" id="fnref:126" href="#fn:126"><sup>126</sup></a> In August 2015, Actavis' request was denied.<a class="footnote-ref" id="fnref:127" href="#fn:127"><sup>127</sup></a> </p> <h2 id="society-and-culture">Society and culture</h2> <h3>Recreational use</h3> <p><a href="/facts/Recreational_use/eoBD3vKn">Recreational use</a> of memantine at supratherapeutic doses has been reported.<a class="footnote-ref" id="fnref:128" href="#fn:128"><sup>128</sup></a> It is a weak <a href="/facts/NMDA_receptor_antagonist/4VJvEpdK">NMDA receptor antagonist</a> and is reported to produce <a href="/facts/Dissociative/5aaD39vM">dissociative</a> and <a href="/facts/Phencyclidine/4LaNo5Cl">phencyclidine</a> (PCP)-like effects in animals and humans at sufficiently high doses.<a class="footnote-ref" id="fnref:129" href="#fn:129"><sup>129</sup></a><a class="footnote-ref" id="fnref:130" href="#fn:130"><sup>130</sup></a><a class="footnote-ref" id="fnref:131" href="#fn:131"><sup>131</sup></a> Even therapeutic doses have been found to produce mild dissociative-like effects in clinical studies.<a class="footnote-ref" id="fnref:132" href="#fn:132"><sup>132</sup></a> In any case, the very long <a href="/facts/Duration_of_action/zdvfFshl">duration of action</a> of memantine (>40 hours) has likely limited its <a href="/facts/Misuse_potential/e3jLXFsF">misuse potential</a>.<a class="footnote-ref" id="fnref:133" href="#fn:133"><sup>133</sup></a> Recreational use of the related drug <a href="/facts/Amantadine/wPfBx4Q4">amantadine</a> has similarly been reported.<a class="footnote-ref" id="fnref:134" href="#fn:134"><sup>134</sup></a> </p><p>A study examining self-reported use of memantine on the social network <a href="/facts/Reddit/PAJjm63I">Reddit</a> showed that the drug was used both recreationally and as a <a href="/facts/Nootropic/XRMFvK7L">nootropic</a>, but also that it was misused in various illnesses as <a href="/facts/Self-medication/wkD9fMtg">self-medication</a> without strong scientific basis.<a class="footnote-ref" id="fnref:135" href="#fn:135"><sup>135</sup></a> </p> <h3>Brand names</h3> <p>As of August 2017, memantine is marketed under many brand names worldwide including Abixa, Adaxor, Admed, Akatinol, Alceba, Alios, Almenta, Alois, Alzant, Alzer, Alzia, Alzinex, Alzixa, Alzmenda, Alzmex, Axura, Biomentin, Carrier, Cogito, Cognomem, Conexine, Cordure, Dantex, Demantin, Demax, Dementa, Dementexa, Ebitex, Ebixa, Emantin, Emaxin, Esmirtal, Eutebrol, Evy, Ezemantis, Fentina, Korint, Lemix, Lindex, Lindex, Lucidex, Manotin, Mantine, Mantomed, Marbodin, Mardewel, Marixino, Maruxa, Maxiram, Melanda, Memabix, Memamed, Memando, Memantin, Memantina, Memantine, Mémantine, Memantinol, Memantyn, Memanvitae, Memanxa, Memanzaks, Memary, Memax, Memexa, Memigmin, Memikare, Memogen, Memolan, Memorel, Memorix, Memotec, Memox, Memxa, Mentikline, Mentium, Mentixa, Merandex, Merital, Mexia, Mimetix, Mirvedol, Modualz, Morysa, Namenda, Nemdatine, Nemdatine, Nemedan, Neumantine, Neuro-K, Neuroplus, Noojerone, Pertam, Polmatine, Prilben, Pronervon, Ravemantine, Talentum, Timantila, Tingreks, Tonibral, Tormoro, Valcoxia, Vilimen, Vivimex, Witgen, Xapimant, Ymana, Zalatine, Zemertinex, Zenmem, Zenmen, and Zimerz.<a class="footnote-ref" id="fnref:136" href="#fn:136"><sup>136</sup></a> </p><p>It is marketed in some countries as a <a href="/facts/Combination_drug/pVS5UD72">combination drug</a> with <a href="/facts/Donepezil/kmCkGdVx">donepezil</a> (<a href="/facts/Memantine%2fdonepezil/4Rv7bjth">memantine/donepezil</a>) under the brand names Namzaric, Neuroplus Dual, and Tonibral MD.<a class="footnote-ref" id="fnref:137" href="#fn:137"><sup>137</sup></a> </p> <h2 id="research">Research</h2> <h3>Psychiatric disorders</h3> <p>Memantine has been studied and used <a href="/facts/Off-label_use/0PDs5VWS">off-label</a> in the treatment of a variety of <a href="/facts/Psychiatric_disorder/EPNjFtFf">psychiatric disorders</a>.<a class="footnote-ref" id="fnref:138" href="#fn:138"><sup>138</sup></a> These include <a href="/facts/Depression_(mood)/GDNFWm1L">depression</a>, <a href="/facts/Bipolar_disorder/aMDwXbV0">bipolar disorder</a>, <a href="/facts/Schizophrenia/FMP4lQ57">schizophrenia</a>, <a href="/facts/Obsessive%25E2%2580%2593compulsive_disorder/bIhDh4dz">obsessive–compulsive disorder</a> (OCD), <a href="/facts/Substance_misuse/e3jLXFsF">substance misuse</a>, <a href="/facts/Pervasive_developmental_disorder/q6pRM03w">pervasive developmental disorders</a> (PDDs), and <a href="/facts/Binge_eating_disorder/4KSgj3BV">binge eating disorder</a> (BED).<a class="footnote-ref" id="fnref:139" href="#fn:139"><sup>139</sup></a> A 2008 <a href="/facts/Systematic_review/dGvq3BGx">systematic review</a> concluded that although it was promising for such uses, memantine could not be recommended for such indications due to inadequate data.<a class="footnote-ref" id="fnref:140" href="#fn:140"><sup>140</sup></a> </p><p>Memantine does not appear to be effective in the treatment of <a href="/facts/Major_depressive_disorder/l2lQeWqr">unipolar major depression</a> or <a href="/facts/Bipolar_depression/aMDwXbV0">bipolar depression</a> on the basis of <a href="/facts/Systematic_review/dGvq3BGx">systematic reviews</a> and <a href="/facts/Meta-analysis/IcfChd8z">meta-analyses</a>, including a 2021 <a href="/facts/Cochrane_review/UlmdJ1H8">Cochrane review</a>.<a class="footnote-ref" id="fnref:141" href="#fn:141"><sup>141</sup></a><a class="footnote-ref" id="fnref:142" href="#fn:142"><sup>142</sup></a><a class="footnote-ref" id="fnref:143" href="#fn:143"><sup>143</sup></a><a class="footnote-ref" id="fnref:144" href="#fn:144"><sup>144</sup></a><a class="footnote-ref" id="fnref:145" href="#fn:145"><sup>145</sup></a> However, a 2022 systematic review and meta-analysis concluded that memantine was significantly effective in the treatment of depressive symptoms in various psychiatric disorders, although with a very small <a href="/facts/Effect_size/mIpNrPte">effect size</a> (<a href="/facts/Hedges%2527_g/mIpNrPte">Hedges' g</a> = -0.17).<a class="footnote-ref" id="fnref:146" href="#fn:146"><sup>146</sup></a> </p><p>There are likewise limited data to support memantine in the treatment of <a href="/facts/Schizophrenia/FMP4lQ57">schizophrenia</a> based on systematic reviews and meta-analyses.<a class="footnote-ref" id="fnref:147" href="#fn:147"><sup>147</sup></a><a class="footnote-ref" id="fnref:148" href="#fn:148"><sup>148</sup></a> However, a 2019 systematic review and meta-analysis reported that memantine was effective in the treatment of the <a href="/facts/Schizophrenia/FMP4lQ57">negative</a> and <a href="/facts/Schizophrenia/FMP4lQ57">cognitive symptoms</a> of schizophrenia with medium to large effect sizes.<a class="footnote-ref" id="fnref:149" href="#fn:149"><sup>149</sup></a> </p> <h3>Parkinson's disease</h3> <p>Memantine has been studied in the treatment of <a href="/facts/Parkinson%2527s_disease/xpekKj6x">Parkinson's disease</a> since the early 1970s.<a class="footnote-ref" id="fnref:150" href="#fn:150"><sup>150</sup></a><a class="footnote-ref" id="fnref:151" href="#fn:151"><sup>151</sup></a><a class="footnote-ref" id="fnref:152" href="#fn:152"><sup>152</sup></a><a class="footnote-ref" id="fnref:153" href="#fn:153"><sup>153</sup></a><a class="footnote-ref" id="fnref:154" href="#fn:154"><sup>154</sup></a> Whereas the related drug <a href="/facts/Amantadine/wPfBx4Q4">amantadine</a> is approved for the treatment of Parkinson's disease and has been since the early 1970s,<a class="footnote-ref" id="fnref:155" href="#fn:155"><sup>155</sup></a> memantine is not approved for the treatment of Parkinson's disease as of 2024.<a class="footnote-ref" id="fnref:156" href="#fn:156"><sup>156</sup></a> However, it has been said that memantine, along with amantadine, has been widely used as an <a href="/facts/Antiparkinsonian_agent/ESoJ5bf5">antiparkinsonian agent</a> since at least 1994.<a class="footnote-ref" id="fnref:157" href="#fn:157"><sup>157</sup></a> </p><p>Although amantadine and memantine have fairly similar <a href="/facts/Pharmacology/4Rx8s7Ie">pharmacology</a>, it has been said that memantine does not share the <a href="/facts/Dyskinesia/2I2MdaSc">antidyskinetic</a> effects of amantadine.<a class="footnote-ref" id="fnref:158" href="#fn:158"><sup>158</sup></a><a class="footnote-ref" id="fnref:159" href="#fn:159"><sup>159</sup></a> However, findings are conflicting, and some data suggest that memantine may also have antidyskinetic effects.<a class="footnote-ref" id="fnref:160" href="#fn:160"><sup>160</sup></a><a class="footnote-ref" id="fnref:161" href="#fn:161"><sup>161</sup></a><a class="footnote-ref" id="fnref:162" href="#fn:162"><sup>162</sup></a> Similarly to amantadine and <a href="/facts/Dopamine_receptor_agonist/T2dH5XUx">dopamine receptor agonists</a>, memantine reverses <a href="/facts/Haloperidol/ue4TJKmu">haloperidol</a>-induced <a href="/facts/Catalepsy/DhnEc8gF">catalepsy</a> and <a href="/facts/Monoamine_depleting_agent/slXFWnoY">monoamine depletion</a>-induced <a href="/facts/Sedation/wFWEChs8">sedation</a> in animals.<a class="footnote-ref" id="fnref:163" href="#fn:163"><sup>163</sup></a><a class="footnote-ref" id="fnref:164" href="#fn:164"><sup>164</sup></a> Memantine has been found to reduce <a href="/facts/Bradykinesia/szUKFDEn">bradykinesia</a> and <a href="/facts/Resting_tremor/rD6ogM7X">resting tremor</a> in people with Parkinson's disease.<a class="footnote-ref" id="fnref:165" href="#fn:165"><sup>165</sup></a><a class="footnote-ref" id="fnref:166" href="#fn:166"><sup>166</sup></a> Memantine and amantadine are said to have moderate <a href="/facts/Akinesia/szUKFDEn">anti-akinetic</a> effects in the treatment of Parkinson's disease.<a class="footnote-ref" id="fnref:167" href="#fn:167"><sup>167</sup></a><a class="footnote-ref" id="fnref:168" href="#fn:168"><sup>168</sup></a> The doses of memantine used for Parkinson's disease are about 5- to 10-fold lower than those of amantadine, which has been attributed to greater <a href="/facts/Potency_(pharmacology)/D38FDyPh">potency</a> of memantine.<a class="footnote-ref" id="fnref:169" href="#fn:169"><sup>169</sup></a> </p><p>As of 2022, a <a href="/facts/Phases_of_clinical_research/o8hEodVu">phase 3</a> <a href="/facts/Clinical_trial/q8LMr832">clinical trial</a> is studying the potential of memantine as <a href="/facts/Disease-modifying_treatment/h3hDQPCX">disease-modifying treatment</a> for Parkinson's disease that might slow progression of the disease.<a class="footnote-ref" id="fnref:170" href="#fn:170"><sup>170</sup></a><a class="footnote-ref" id="fnref:171" href="#fn:171"><sup>171</sup></a><a class="footnote-ref" id="fnref:172" href="#fn:172"><sup>172</sup></a> It is specifically theorized to act by inhibiting cell-to-cell transmission of <a href="/facts/%25CE%2591-synuclein/rMau6thf">α-synuclein</a>.<a class="footnote-ref" id="fnref:173" href="#fn:173"><sup>173</sup></a><a class="footnote-ref" id="fnref:174" href="#fn:174"><sup>174</sup></a> </p><p>Besides Parkinson's disease, memantine has been studied in the treatment of <a href="/facts/Parkinson%2527s_disease_dementia/nE8dqpLP">Parkinson's disease dementia</a> (PDD) and <a href="/facts/Dementia_with_Lewy_bodies/Sw6vTGkh">dementia with Lewy bodies</a> (DLB).<a class="footnote-ref" id="fnref:175" href="#fn:175"><sup>175</sup></a><a class="footnote-ref" id="fnref:176" href="#fn:176"><sup>176</sup></a><a class="footnote-ref" id="fnref:177" href="#fn:177"><sup>177</sup></a> </p> <h3>Apathy</h3> <p>Apathy is a <a href="/facts/Disorder_of_diminished_motivation/wboM9IgT">disorder of diminished motivation</a> characterized by diminished interest and activity.<a class="footnote-ref" id="fnref:178" href="#fn:178"><sup>178</sup></a><a class="footnote-ref" id="fnref:179" href="#fn:179"><sup>179</sup></a> <a href="/facts/Systematic_review/dGvq3BGx">Systematic reviews</a> and <a href="/facts/Meta-analysis/IcfChd8z">meta-analyses</a> published from 2016 to 2022 have found that memantine is not effective in the treatment of <a href="/facts/Apathy/1Vp2zGnn">apathy</a> in Alzheimer's disease and other <a href="/facts/Dementia/T0MRDE9I">dementias</a>.<a class="footnote-ref" id="fnref:180" href="#fn:180"><sup>180</sup></a><a class="footnote-ref" id="fnref:181" href="#fn:181"><sup>181</sup></a><a class="footnote-ref" id="fnref:182" href="#fn:182"><sup>182</sup></a> However, another 2022 review reported that it was effective.<a class="footnote-ref" id="fnref:183" href="#fn:183"><sup>183</sup></a> </p> <h3>Long COVID</h3> <p>Memantine, along with <a href="/facts/Amantadine/wPfBx4Q4">amantadine</a>, is being studied and used <a href="/facts/Off-label_use/0PDs5VWS">off-label</a> in the treatment <a href="/facts/Long_COVID/9YQdUEE2">long COVID</a>.<a class="footnote-ref" id="fnref:184" href="#fn:184"><sup>184</sup></a><a class="footnote-ref" id="fnref:185" href="#fn:185"><sup>185</sup></a> </p> <h3>Catatonia</h3> <p>Memantine, along with <a href="/facts/Amantadine/wPfBx4Q4">amantadine</a>, has been reported to be effective in the treatment of <a href="/facts/Catatonia/7agpD58W">catatonia</a> in <a href="/facts/Case_report/gIQnMGCR">case reports</a> and <a href="/facts/Case_series/2NQBzYJK">case series</a>.<a class="footnote-ref" id="fnref:186" href="#fn:186"><sup>186</sup></a><a class="footnote-ref" id="fnref:187" href="#fn:187"><sup>187</sup></a><a class="footnote-ref" id="fnref:188" href="#fn:188"><sup>188</sup></a> </p> <h3>Autism</h3> <p>Effects in <a href="/facts/Autism/6MTwMNoJ">autism</a> are unclear.<a class="footnote-ref" id="fnref:189" href="#fn:189"><sup>189</sup></a><a class="footnote-ref" id="fnref:190" href="#fn:190"><sup>190</sup></a> </p> <h2 id="further-reading">Further reading</h2> <ul><li>Lipton SA (April 2005). "The molecular basis of memantine action in Alzheimer's disease and other neurologic disorders: low-affinity, uncompetitive antagonism". <i>Current Alzheimer Research</i>. 2 (2): 155–165. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.2174%2F1567205053585846">10.2174/1567205053585846</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/15974913">15974913</a>.</li></ul> <h2 id="references">References</h2> <ol> <li id="fn:1"><p>"Memantine Hydrochloride Monograph for Professionals". Drugs.com. American Society of Health-System Pharmacists. Archived from the original on 25 April 2019. Retrieved 3 March 2019. <a href="https://www.drugs.com/monograph/memantine-hydrochloride.html" target="_blank">https://www.drugs.com/monograph/memantine-hydrochloride.html</a> <a href="#fnref:1" class="footnote-back-ref">↩</a></p></li> <li id="fn:2"><p>British national formulary : BNF 76 (76 ed.). Pharmaceutical Press. 2018. pp. 303–304. ISBN 9780857113382. <a href="9780857113382" target="_blank">9780857113382</a> <a href="#fnref:2" class="footnote-back-ref">↩</a></p></li> <li id="fn:3"><p>Alam S, Lingenfelter KS, Bender AM, Lindsley CW (September 2017). "Classics in Chemical Neuroscience: Memantine". ACS Chem Neurosci. 8 (9): 1823–1829. doi:10.1021/acschemneuro.7b00270. PMID 28737885. <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:3" class="footnote-back-ref">↩</a></p></li> <li id="fn:4"><p>"Memantine Hydrochloride Monograph for Professionals". Drugs.com. American Society of Health-System Pharmacists. Archived from the original on 25 April 2019. Retrieved 3 March 2019. <a href="https://www.drugs.com/monograph/memantine-hydrochloride.html" target="_blank">https://www.drugs.com/monograph/memantine-hydrochloride.html</a> <a href="#fnref:4" class="footnote-back-ref">↩</a></p></li> <li id="fn:5"><p>Alam S, Lingenfelter KS, Bender AM, Lindsley CW (September 2017). "Classics in Chemical Neuroscience: Memantine". ACS Chem Neurosci. 8 (9): 1823–1829. doi:10.1021/acschemneuro.7b00270. PMID 28737885. <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>"Memantine Hydrochloride Monograph for Professionals". Drugs.com. American Society of Health-System Pharmacists. Archived from the original on 25 April 2019. Retrieved 3 March 2019. <a href="https://www.drugs.com/monograph/memantine-hydrochloride.html" target="_blank">https://www.drugs.com/monograph/memantine-hydrochloride.html</a> <a href="#fnref:6" class="footnote-back-ref">↩</a></p></li> <li id="fn:7"><p>British national formulary : BNF 76 (76 ed.). Pharmaceutical Press. 2018. pp. 303–304. ISBN 9780857113382. <a href="9780857113382" target="_blank">9780857113382</a> <a href="#fnref:7" class="footnote-back-ref">↩</a></p></li> <li id="fn:8"><p>British national formulary : BNF 76 (76 ed.). Pharmaceutical Press. 2018. pp. 303–304. ISBN 9780857113382. <a href="9780857113382" target="_blank">9780857113382</a> <a href="#fnref:8" class="footnote-back-ref">↩</a></p></li> <li id="fn:9"><p>Alam S, Lingenfelter KS, Bender AM, Lindsley CW (September 2017). "Classics in Chemical Neuroscience: Memantine". ACS Chem Neurosci. 8 (9): 1823–1829. doi:10.1021/acschemneuro.7b00270. 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