Octahydro-pyrrolo[3,4-b]pyrrole derivatives or a pharmaceutically acceptable salt, ester, amide, prodrug, or radiolabeled form thereof, wherein R 1 is alkyl, C 3 -C 5 cycloalkyl. or (C 3 -C 5 cycloalkyl)methyl; R 2a , R 2b , R 2c , R 2d , R 2e , and R 2f each are independently hydrogen, methyl, or fluoromethyl; R 3a , R 3b , R 3c , and R 3d each are independently hydrogen, alkyl, fluoroalkyl, fluoroalkoxy, alkoxy, thioalkoxy, halogen, or nitrile, with the proviso that when one or more of R 3a , R 3b , R 3c , and R 3d are alkyl, then at least one of R 3a , R 3b , R 3c , and R 3d is fluoroalkyl, fluoroalkoxy, alkoxy, thioalkoxy, halogen, or nitrile; L 1 is a bond, oxygen, sulfur, carbonyl, alkylene,. alkylcarbonyl, alkylamino, -C(=N-Oalkyl)-, NR 4 , -C(=O) NR 4 -, or -NR4C(=O)-; R 4 is hydrogen or alkyl; Cy 1 is aryl, cycloalkyl, cycloalkenyl, heteroaryl, or heterocycle; Z is a substituent R 6 or a group represented by -L 3 -Cy 3 ; R 6 is hydrogen, acyl, acyloxy, alkenyl, alkoxy, alkoxyalkoxy, alkoxyalkyl, alkoxycarbonyl, alkoxyimino, alkoxysulfonyl, alkyl, alkylcarbonyl, alkylsulfonyl, alkynyl, amido, carboxy, cyano, cycloalkyl, fiuoroalkoxy, haloalkoxy, haloalkyl, halogen, hydroxy, hydroxyalkyl, mercapto, nitro, alkylthio, amino, NHR 7 , NR 7 R 8 , -N(R 7 )C(=O)R 9 , -C(=O)NR 7 R 8 , or N(R 7 )SO 2 (R 10 ); L 3 is a bond, oxygen, sulfur, carbonyl, alkylene, alkylcarbonyl, alkylamino, -C(=N-Oalkyl)-, NR 11 , -C(=O) NR 11 -, or -NR 11 C(=O)-;Cy 3 is aryl, cycloalkyl, cycloalkenyl, heteroaryl, or heterocycle; R 7 , R 8 , R 9 , R 10 , and R 11 at each occurrence are independently hydrogen,C 1-4 alkyl, C 3 -C 4 cycloalkyl, or a (C 3 -C 4 cycloalkyl)amine; are useful in treating conditions or disorders prevented by or ameliorated by histamine-3 receptor ligands. Octahydro-pyrrolo[3,4-b]pyrrole compounds, methods for using such compounds, compositions for making them, and processes for preparing such compounds are disclosed herein.