Inhibition of choline uptake by N-cyclohexylcholine, a high affinity ligand for the choline transporter at the blood-brain barrier

Journal of Drug Targeting

Volumn 13, Issue 4, 2005, Pages 259-266

  Geldenhuys, Werner J ^a   Lockman, Paul R ^a   Philip, Ashok E ^b   McAfee, James H ^a   Miller, Bryan L ^b   McCurdy, Christopher R ^b,c   Allen, David D ^a  

^a TEXAS TECH UNIVERSITY HEALTH SCIENCES CENTER   (United States)

^b UNIVERSITY OF MISSISSIPPI   (United States)

^c UNIVERSITY OF MISSISSIPPI   (United States)

Author keywords

BBB choline transporter; CHT; Drug delivery; Drug design; Molecular modelling; SYBYL

Indexed keywords

CARRIER PROTEIN; CHOLINE; CHOLINE DERIVATIVE; NITROGEN;

ANIMAL TISSUE; ARTICLE; BINDING AFFINITY; BINDING KINETICS; BLOOD BRAIN BARRIER; BRAIN PERFUSION; CENTRAL NERVOUS SYSTEM; CHOLINE UPTAKE; COMPARATIVE MOLECULAR FIELD ANALYSIS; COMPUTER MODEL; CONTROLLED STUDY; DRUG DELIVERY SYSTEM; DRUG STRUCTURE; DRUG TARGETING; HYDROPHOBICITY; INHIBITION KINETICS; MALE; NONHUMAN; PILOT STUDY; PRIORITY JOURNAL; RAT;

ANIMALS; BIOLOGICAL TRANSPORT; BLOOD-BRAIN BARRIER; CHOLINE; DRUG CARRIERS; LIGANDS; MALE; MODELS, MOLECULAR; MOLECULAR STRUCTURE; NERVE TISSUE PROTEINS; PILOT PROJECTS; PLASMA MEMBRANE NEUROTRANSMITTER TRANSPORT PROTEINS; PROTEIN BINDING; RATS; RATS, INBRED F344; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 23244449089     PISSN: 1061186X     EISSN: None     Source Type: Journal    
DOI: 10.1080/10611860500139222     Document Type: Article

References (22)

1. Allen DD. 1994. Assessment of blood-brain barrier choline transporter using the in situ brain perfusion technique. Soc Neurosci Abstr 20:1334.
2. Allen DD, Lockman PR. 2003. The blood-brain barrier choline transporter as brain drug delivery vector. Life Sci 73:1609-1615.
3. Allen DD, Smith QR. 1999. Blood-brain barrier choline transport in the senescent rat. Neurosci Lett 277:198-202.
4. Allen DD, Smith QR. 2001. Characterization of the blood-brain barrier choline transporter using the in-situ rat brain perfusion technique. J Neurochem 76:1-11.
5. Allen DD, Lockman PR, Roder KE, Dwoskin LP, Crooks PA. 2003. Active transport of high affinity choline and nicotine analogs into the central nervous system by the blood-brain barrier choline transporter. J Pharmacol Exp Ther 304:1268-1274.
6. Calas M, Cordina G, Bompart J, Ben Bari M, Jei T, Ancelin ML, Vial H. 1997. Antimalarial activity of molecules interfering with Plasmodium falciparum phospholipid metabolism. Structure-activity relationship analysis. J Med Chem 40:3557-3566.
7. Geldenhuys WJ, Lockman PR, McAfee JH, Fitzpatrick KT, Van der Schyf CJ, Allen DD. 2004. Molecular modeling studies on the active binding site of the blood-brain barrier choline transporter. Bioorg Med Chem Lett 14:3085-3092.
8. Goldenberg GJ, Begleiter A. 1979. Membrane transport of alkylating agents. Pharmacol Ther 6:237-274.
9. Greig NH. 1989. Drug delivery to the brain by blood-brain barrier circumvention and drug modification. In: Neuwelt EA, editor. Implications of the blood-brain barrier and its manipulation. New York: Plenum Press. p 311-367.
10. Kim KH, Greco G, Novellino E. 1998. A critical review of recent CoMFA applications. Perspectives in drug discovery and design. 12/13/14. p 257-315.
11. Lerner J. 1989. Choline transport specificity in animal cells and tissues. Comp Biochem Physiol 93:1-9.
12. Lindborg B, Crona K, Dahlbom R, Ross SB. 1984. Troxonium-like inhibitors of the high affinity uptake of choline in mouse brain synaptosomes in vitro. Acta Pharmaceutica Suecica 21:271-294.
13. Lockman PR, Allen DD. 2002. The transport of choline. Drug Dev Ind Pharm 28:749-771.
14. Lockman PR, Koziara JR, Paulson J, Abbruscato TJ, Mumper RJ, Allen DD. 2003. In-vivo and in-vitro assessment of baseline blood-brain barrier parameters in the presence of novel nanoparticles. Pharm Res 20:705-713.
15. Metting TL, Burgio DE, Terry AV, Beach JW, McCurdy CR, Allen DD. 1998. Inhibition of brain choline uptake by isoarecolone and lobeline derivatives: Implications for potential vector-mediated brain drug delivery. Neurosci Lett 258:25-28.
16. Pardridge WM. 2002. Drug and gene targeting to the brain with molecular Trojan horses. Nat Rev Drug Discov 1:131-139.
17. Slavachevskaya NM, Belen'kaya IA, Tsepova NS, Levocheskaya EI, Krasil'nikov II. 1976. Synthesis of some quaternary derivatives in the series of aminophenol and 2,1,3-benzothiadiazole used as potential radioprotective, agents. USSR Khimiko-Farmatsevticheskii Zhurnal 10:53-58.
18. Smith QR. 1993. Drug delivery to brain and the role of carrier-mediated transport. Adv Exp Med Biol 331:83-93.
19. Smith QR. 1996. Brain perfusion systems for studies of drug uptake and metabolism in the central nervous system. Pharm Biotechnol 8:285-307.
20. Takasato Y, Rapoport SI, Smith QR. 1984. An in-situ brain perfusion technique to study cerebrovascular transport in the rat. Am J Physiol 247:484-493.
21. Tamai I, Tsuji A. 2000. Transporter-mediated permeation of drugs across the blood-brain barrier. J Pharm Sci 89:1371-1388.
22. Tamaru M, Roberts E. 1988. Structure-activity studies on inhibition of choline uptake by a mouse brain synaptosomal preparation: Basic data. I. Brain Res 473:205-226.