1. In vivo characterization of a novel phenylisothiocyanate tropane analog at monoamine transporters in rat brain
Vishakantha Murthy, Thomas J Martin, Susy Kim, Huw M L Davies, Steven R Childers J Pharmacol Exp Ther. 2008 Aug;326(2):587-95. doi: 10.1124/jpet.108.138842. Epub 2008 May 20.
Previous studies have shown that the phenylisothiocyanate tropane analog 2-beta-propanoyl-3-beta-(2-naphthyl)-8-[4-isothiocyanato)benzyl]nortropane (HD-205) binds covalently to dopamine and serotonin transporters (DAT and SERT, respectively) in rat brain membranes (Biochem Pharmacol 74:336-344, 2007). The present study evaluated the irreversible effects of HD-205 in vivo in rats after intracranial injection. Rats were implanted with unilateral cannulae in rat striatum, and HD-205 (0.001-3 nmol) was administered by intrastriatal injection. In vitro autoradiography of DAT binding with [125I]2-carbomethoxy-3-(4-iodophenyl)tropane (RTI-55) on brain sections obtained 24 h after injection showed a highly localized blockade of binding in striatum, with maximal blockade of binding by 1 to 3 nmol HD-205. Similar blockade of SERT binding (using [3H]-citalopram) was observed in the same area. No blockade of DAT or SERT binding was observed after intrastriatal injections of the reversible analog 2-beta-propanoyl-3-beta-(2-naphthyl)-8-benzyl nortropane (HD-206), and HD-205 treatment had no effect on D(2)- and mu-opioid-stimulated guanosine 5'-O-(3-[35S]thio)-triphosphate binding in sections from the same animals. In a time course study, rats administered with 1 nmol HD-205 showed recovery of 50% DAT binding after 3 to 4 days postinjection, and full recovery after 6 weeks. Rats implanted with bilateral cannulae were tested for cocaine-induced locomotor activity. Two days after intrastriatal injection of 1 nmol of HD-205, systemic (20 mg/kg i.p.) cocaine-induced locomotor activity was not affected; however, locomotor activity induced by intrastriatal administration of cocaine (6 nmol) was eliminated. This strategy of site-specific chemical blockade of transporters could serve as a valuable tool to evaluate the neuroanatomical basis of DAT-mediated cocaine effects.
2. Synthesis and microbiological activities of beta-(1-chloro-2-naphthyl) alanine and beta-(1-bromo-2-naphthyl) alanine
T J McCord, R N Watson, C E DuBose, K L Hulme, A L Davis J Med Chem. 1976 Mar;19(3):429-30. doi: 10.1021/jm00225a020.
beta-(1-Chloro-2-naphthyl)alanine and beta-(1-bromo-2-naphthyl) alanine were synthesized by ammonolysis of the corresponding alpha, 1-dihalo-2-naphthalenepropanoic acids derived from 1-nitro-2-naphthylamine by diazotization and condensation with acrylic acid in the presence of cuprous halides. The two analogs as well as the previously reported beta-(2-naphthyl)alanine and beta-(1-naphthyl)alanine were studied as growth inhibitors of Escherichia coli 9723, Leuconostoc dextranicum 8086, and Lactobacillus plantarum 8014. In general, the chloro and bromo analogs were more effective than the unsubstituted naphthylalanines as growth inhibitors of the three microorganisms studied.
3. Labeling peptides with rhenium-188
L Meléndez-Alafort, G Ferro-Flores, C Arteaga-Murphy, M Pedraza-López, M A González-Zavala, J I Tendilla, L García-Salinas Int J Pharm. 1999 May 25;182(2):165-72. doi: 10.1016/s0378-5173(99)00054-x.
A direct labeling technique via EHDP for the preparation of 188Re-somatostatin analogue peptide beta-(2-naphthyl)-D-Ala-Cys-Tyr-D-Trp-Lys-Val-Cys-Thr-amide complex was developed. The influence of reaction conditions such as pH, temperature, weak ligand concentration and stannous chloride concentration were investigated. Methods of analysis were also established permitting identification of radiochemical impurities which may be present in the radiopharmaceutical solution. Results showed that under the procedure reported herein 188Re-peptide complex can be prepared with a radiochemical purity of 90% and a specific activity up to 1.8 GBq mg-1 without radiolytic degradation of the product.
