The novel pyrrolidine nor-lobelane analog UKCP-110 [cis-2,5-di-(2- phenethyl)-pyrrolidine hydrochloride] inhibits VMAT2 function, methamphetamine-evoked dopamine release, and methamphetamine self-administration in rats

Journal of Pharmacology and Experimental Therapeutics

Volumn 335, Issue 3, 2010, Pages 841-851

  Beckmann, Joshua S ^a   Siripurapu, Kiran B ^b   Nickell, Justin R ^b   Horton, David B ^b   Denehy, Emily D ^a   Vartak, Ashish ^b   Crooks, Peter A ^b   Dwoskin, Linda P ^b   Bardo, Michael T ^a  

^a 1615 Patterson Office Tower   (United States)

^b Division of Pharmacy Practice and Science   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

2,5 BIS(2 PHENETHYL)PYRROLIDINE; BIS(2 PHENETHYL)PYRROLIDINE; BIS(2 PHENETHYL)PYRROLIDINE HYDROCHLORIDE; DIHYDROTETRABENAZINE; DIHYDROXYPHENYLACETIC ACID; LOBELANE; LOBELINE; METHAMPHETAMINE; METHYLLYCACONITINE; NICOTINE; NICOTINIC RECEPTOR; NORLOBELANE; PYRROLIDINE DERIVATIVE; UKCP 110; UKCP 111; UKCP 112; UNCLASSIFIED DRUG; VESICULAR MONOAMINE TRANSPORTER 2;

ANIMAL CELL; ANIMAL EXPERIMENT; ARTICLE; BINDING AFFINITY; CONTROLLED STUDY; CORPUS STRIATUM; DOPAMINE RELEASE; DOPAMINE UPTAKE; DRUG ABUSE; DRUG BINDING; DRUG INHIBITION; DRUG POTENCY; DRUG RECEPTOR BINDING; DRUG SELF ADMINISTRATION; FOOD INTAKE; IC 50; MALE; METHAMPHETAMINE ABUSE; NONHUMAN; PRIORITY JOURNAL; RAT; REINFORCEMENT; SYNAPSE VESICLE; TRANS ISOMER;

3,4-DIHYDROXYPHENYLACETIC ACID; ACONITINE; AMPHETAMINE-RELATED DISORDERS; ANIMALS; BEHAVIOR, ANIMAL; CELL MEMBRANE; CONDITIONING, OPERANT; CORPUS STRIATUM; DOPAMINE; DRUG TOLERANCE; LOBELINE; MALE; METHAMPHETAMINE; NICOTINE; PROTEIN BINDING; PYRROLIDINES; RATS; RATS, SPRAGUE-DAWLEY; RECEPTORS, NICOTINIC; REINFORCEMENT (PSYCHOLOGY); SELF ADMINISTRATION; SYNAPTIC VESICLES; TETRABENAZINE; VESICULAR MONOAMINE TRANSPORT PROTEINS;

EID: 78649627100     PISSN: 00223565     EISSN: 15210103     Source Type: Journal    
DOI: 10.1124/jpet.110.172742     Document Type: Article

References (32)

1. Baumann MH, Phillips JM, Ayestas MA, Ali SF, Rice KC, and Rothman RB (2002) Preclinical evaluation of GBR12909 decanoate as a long-acting medication for methamphetamine dependence. Ann NY Acad Sci 965:92-108.
2. Benwell ME and Balfour DJ (1998) The influence of lobeline on nucleus accumbens dopamine and locomotor responses to nicotine in nicotine-pretreated rats. Br J Pharmacol 125:1115-1119.
3. Cheng Y and Prusoff WH (1973) Relationship between the inhibition constant (K1) and the concentration of inhibitor which causes 50 per cent inhibition (I50) of an enzymatic reaction. Biochem Pharmacol 22:3099-3108.
4. Decker MW, Brioni JD, Bannon AW, and Arneric SP (1995) Diversity of neuronal nicotinic acetylcholine receptors: lessons from behavior and implications for CNS therapeutics. Life Sci 56:545-570.
5. Dews PB (1958) Studies on behavior. IV. Stimulant actions of methamphetamine. J Pharmacol Exp Ther 122:137-147.
6. Donny EC, Caggiula AR, Knopf S, and Brown C (1995) Nicotine self-administration in rats. Psychopharmacology (Berl) 122:390-394.
7. Dwoskin LP and Crooks PA (2002) A novel mechanism of action and potential use for lobeline as a treatment for psychostimulant abuse. Biochem Pharmacol 63:89-98.
8. Dwoskin LP, Wooters TE, Sumithran SP, Siripurapu KB, Joyce BM, Lockman PR, Manda VK, Ayers JT, Zhang Z, Deaciuc AG, et al. (2008) N,N′-Alkane- diyl-bis-3- picoliniums as nicotinic receptor antagonists: inhibition of nicotine-evoked dopamine release and hyperactivity. J Pharmacol Exp Ther 326:563-576.
9. Fudala PJ and Iwamoto ET (1986) Further studies on nicotine-induced conditioned place preference in the rat. Pharmacol Biochem Behav 25:1041-1049.
10. Fumagalli F, Gainetdinov RR, Wang YM, Valenzano KJ, Miller GW, and Caron MG (1999) Increased methamphetamine neurotoxicity in heterozygous vesicular monoamine transporter 2 knock-out mice. J Neurosci 19:2424-2431. (Pubitemid 29162392)
11. Gnegy ME (2003) The effect of phosphorylation on amphetamine-mediated outward transport. Eur J Pharmacol 479:83-91.
12. Harrod SB, Dwoskin LP, Crooks PA, Klebaur JE, and Bardo MT (2001) Lobeline attenuates D-methamphetamine self-administration in rats. J Pharmacol Exp Ther 298:172-179.
13. Harrod SB, Dwoskin LP, Green TA, Gehrke BJ, and Bardo MT (2003) Lobeline does not serve as a reinforcer in rats. Psychopharmacology (Berl) 165:397-404.
14. Le Foll B and Goldberg SR (2005) Nicotine induces conditioned place preferences over a large range of doses in rats. Psychopharmacology (Berl) 178:481-492.
15. + efflux from thalamic synaptosomes. Neuropharmacology 39:2654-2662.
16. Miller DK, Crooks PA, Teng L, Witkin JM, Munzar P, Goldberg SR, Acri JB, and Dwoskin LP (2001) Lobeline inhibits the neurochemical and behavioral effects of amphetamine. J Pharmacol Exp Ther 296:1023-1034.
17. Miller DK, Crooks PA, Zheng G, Grinevich VP, Norrholm SD, and Dwoskin LP (2004) Lobeline analogs with enhanced affinity and selectivity for plasmalemma and vesicular monoamine transporters. J Pharmacol Exp Ther 310:1035-1045.
18. Munzar P and Goldberg SR (2000) Dopaminergic involvement in the discriminative-stimulus effects of methamphetamine in rats. Psychopharmacology (Berl) 148: 209-216.
19. Munzar P, Baumann MH, Shoaib M, and Goldberg SR (1999) Effects of dopamine and serotonin-releasing agents on methamphetamine discrimination and self-administration in rats. Psychopharmacology (Berl) 141:287-296.
20. Neugebauer NM, Harrod SB, Stairs DJ, Crooks PA, Dwoskin LP, and Bardo MT (2007) Lobelane decreases methamphetamine self-administration in rats. Eur J Pharmacol 571:33-38.
21. Neugebauer NM, Zhang Z, Crooks PA, Dwoskin LP, and Bardo MT (2006) Effect of a novel nicotinic receptor antagonist, N,N′-dodecane-1,12-diyl-bis-3- picolinium dibromide, on nicotine self-administration and hyperactivity in rats. Psychopharmacology (Berl) 184:426-434.
22. Nickell JF, Krishnamurthy S, Norrholm S, Deaciuc G, Siripurapu KB, Zheng G, Crooks PA, and Dwoskin LP (2010) Lobelane inhibits methamphetamine-evoked dopamine release via inhibition of the vesicular monoamine transporter-2. J Pharmacol Exp Ther 332:612-621.
23. Schneider FH and Olsson TA (1996) Clinical experience with lobeline as a smoking cessation agent. Med Chem Res 6:562-570.
24. Schuster CR, Fischman MW, and Johanson CE (1981) Internal stimulus control and subjective effects of drugs. NIDA Res Monogr 37:116-129.
25. Sulzer D, Chen TK, Lau YY, Kristensen H, Rayport S, and Ewing A (1995) Amphetamine redistributes dopamine from synaptic vesicles to the cytosol and promotes reverse transport. J Neurosci 15:4102-4108.
26. Takahashi N, Miner LL, Sora I, Ujike H, Revay RS, Kostic V, Jackson-Lewis V, Przedborski S, and Uhl GR (1997) VMAT2 knockout mice: heterozygotes display reduced amphetamine-conditioned reward, enhanced amphetamine locomotion, and enhanced MPTP toxicity. Proc Natl Acad Sci USA 94:9938-9943.
27. 3H]dopamine from rat striatal synaptic vesicles: comparison with D-amphetamine. J Neurochem 71:258-265.
28. 3H]overflow from rat striatal slices preloaded with [3H]dopamine: differential inhibition of synaptosomal and vesicular [3H]dopamine uptake. J Pharmacol Exp Ther 280:1432-1444.
29. Vartak AP, Nickell JR, Chagkutip J, Dwoskin LP, and Crooks PA (2009) Pyrrolidine analogs of lobelane: relationship of affinity for the tetrabenazine binding site on the vesicular monoamine transporter 2 (VMAT2) with function of VMAT2. J Med Chem 52:7878-7882.
30. Wang YM, Gainetdinov RR, Fumagalli F, Xu F, Jones SR, Bock CB, Miller GW, Wightman RM, and Caron MG (1997) Knockout of the vesicular monoamine transporter 2 gene results in neonatal death and supersensitivity to cocaine and amphetamine. Neuron 19:1285-1296.
31. Wooters TE and Bardo MT (2007) The monoamine oxidase inhibitor phenelzine enhances the discriminative stimulus effect of nicotine in rats. Behav Pharmacol 18:601-608.
32. Zheng G, Dwoskin LP, Deaciuc AG, and Crooks PA (2008) Synthesis and evaluation of a series of homologues of lobelane at the vesicular monoamine transporter-2. Bioorg Med Chem Lett 18:6509-6512.