Methods of using avermectin compositions for the treatment of neurological disorders and dosing regimens

A method of treating or preventing a neurological disorder, the method comprising administering to a subject in need thereof a pharmaceutical composition comprising:

• (i) about 1% to about 15% of a compound, wherein the compound is a compound of Formula I:
• or a pharmaceutically acceptable salt, stereoisomer, polymorph, solvate, or isotopically labeled compound thereof, wherein
• each occurrence of X is independently selected from —CH2—, —NH—, —O—, —S—, —SO— and —SO2—;
• Y is selected from —CH2—, —O—, —NH—, and —S—;
• Z is selected from O and S;
• each occurrence of is a single bond or a double bond;
• n is an integer 0-6;
• and
• each occurrence of R1 is independently selected from halogen, —R, —OR, —NO2, —NCS, —CN, —CF3, —OCF3, —NHR, —N(R)2, —OC(O)R, —C(O)OR, —SR, —C(O)R, —C(O)C(O)R, —C(O)CH2C(O)R, —C(S)R, —C(S)OR, —C(O)C(O)OR, —C(O)C(O)N(R)2, —C(O)N(R)2, —OC(O)N(R)2, —C(S)N(R)2, —N(R)C(O)OR, —N(R)C(O)R, —N(R)C(S)R, —N(R)C(O)N(R)2, —N(R)C(S)N(R)2, —N(COR)COR, —N(OR)R, —C(═NH)N(R)2, —C(O)N(OR)R, —C(═NOR)R, —OP(O)(OR)2, —P(O)(R)2, —P(O)(OR)2, —P(O)(H)(OR), —CH2—OR, and —CH2—O—CH2—R;
• each occurrence of R2 is independently selected from independently selected from H, OH, O—C1-4alkyl, —OC(O)C1-4alkyl, —OC(O)NH2, and —OC(O)NHC1-4alkyl;
• each occurrence of R3 is mono, di, or triglycoside, or OC(O)—(C3-C5)alkenyl;
• each R is independently selected from H, —(C1-C12)alkyl, —(C3-C10)-cycloalkyl, (C3-C10)-cycloalkenyl, —[(C3-C10)cycloalkyl]-(C1-C12)alkyl, —[(C3-C10)cycloalkenyl]-(C1-C12)alkyl, —[(C3-C10)cycloalkenyl]-(C1-C12)alkyl, —[(C3-C10)cycloalkyl]-O—(C1-C12)alkyl, —[(C3-C10)cycloalkenyl]-O—(C1-C12)alkyl, —(C6-C10)aryl, (C6-C10)aryl-(C1-C12)alkyl, —(C6-C10)aryl-O—(C1-C12)alkyl, (C6-C10)aryl-N(R″)—(C1-C12)alkyl, 3- to 10-membered heterocyclyl, (3- to 10-membered heterocyclyl)-(C1-C12)alkyl, (3- to 10-membered heterocyclyl)-O—(C1-C12)alkyl, (3- to 10-membered heterocyclyl)-N(R″)—(C1-C12)alkyl, 5- to 10-membered heteroaryl, (5- to 10-membered heteroaryl)-(C1-C12)-alkyl, (5- to 10-membered heteroaryl)-O—(C1-C12)-alkyl and (5- to 10-membered heteroaryl)-N(R″)—(C1-C12)-alkyl;
• each heterocyclyl has 1-4 heteroatoms independently selected from N, NH, O, S, SO, and SO2, and
• heteroaryl has 1-4 heteroatoms independently selected from N, NH, O, and S;
• each occurrence of R is independently unsubstituted or is substituted with 1 to 5 R′;
• each occurrence of R′ is halo, OH, oxo, —CH2OR″, —CH2N(R″)2, C(O)N(R″)2, —C(O)OR″, —NO2, —NCS, —CN, —CF3, —OCF3 and —N(R″)2;
• and
• each occurrence of R″ is independently H, C1-6 alkyl, C2-6 alkenyl, C3-6 cycloalkyl, C3-6 cycloalkenyl, 3- to 6-membered heterocyclyl, 5- to 10-membered heteroaryl, and (C6-C10)-aryl;
• (ii) about 20% to about 40% of a first surfactant comprising one or more of:
• (a) mono-, di-, and/or tri-fatty acid esters of glycerol;
• (b) mono- and/or di-fatty acid esters of 1,2-propylene glycol;
• and
• (c) mono- and/or di-fatty acid esters of polyethylene glycol wherein the fatty acids are selected from C6 to C10 fatty acids;
• and
• (iii) about 15% to about 70% of a second surfactant selected from one or more of a polysorbate surfactant and/or a fatty acid ester of sorbitan.