References on the Administration of Anticonvulsive Agents Using ALZET® Osmotic Pumps

(For additional anticonvulsants please refer to benzodiazepines list: BENZ)

1. Carbamazepine

10518 Cain, S.M., Ruest, T., Pimlott, S., Patterson, J., Duncan, R., Dewar, D., Sills, G.J. High resolution micro-SPECT scanning in rats using 125I beta-CIT: Effects of chronic treatment with carbamazepine. Epilepsia 2009; 50(-8-):1962-1970. >>> Carbamazepine; DMSO; propylene glycol; ethyl alcohol; acetone; SC; Rat; 2ML2; Controls received mp w/ vehicle; animal info (adult, male, Sprague-Dawley, 160-270 g); functionality of mp verified by serum drug levels; 42% DMSO used; identified 3 mg/kg/day as the highest dose that could be reliably administered via minipumps over a 14-day period at 37 degrees Celsius, pg. 1969.

5323 Doheny, H.C., Jefferys, J.G.R., Whittington, M.A., Patsalos, P.N. A comparison of the efficacy of carbamazepine and the novel anti-epileptic drug levetiracetam in the tetanus toxin model of focal complex partial epilepsy. British Journal of Pharmacology 2002; 135(-6-):1425-1434. >>> Carbamazepine; levetiracetam; DMSO; Propylene glycol; ethanol, saline; IP; Rat; Controls received mp/ vehicle; functionality of mp verified by drug serum levels; dose-response (text p.1428); carbamazepine was dissolved in 42.5% DMSO/42% Propylene glycol/15% ethanol. Levitiracetam was dissolved in saline; 2-day recovery period given using coiled PE-40 tubing; epilepsy; anticonvulsant.

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2. Deprenyl

9614 Chenu, F., El Mansari, M., Blier, P. Long-term administration of monoamine oxidase inhibitors alters the firing rate and pattern of dopamine neurons in the ventral tegmental area. INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY 2009; 12(-4-):475-485. >>> Clorgyline; phenelzine; deprenyl; SC; Rat; Controls received mp w/ saline; enzyme inhibitor (MAO, monoamine oxidase); animal info (male, Sprague Dawley, 250-300 g.).

5573 Mejia, J.M., Ervin, F.R., Baker, G.B., Palmour, R.M. Monoamine oxidase inhibition during brain development induces pathological aggressive behavior in mice. Biological Psychiatry 2002; 52(-8-):811-822. >>> Chlorgyline; Deprenyl; Saline; SC; Mice (pregnant); 2002; 2004; Controls received mp w/ vehicle; teratology; enzyme inhibitors (monoamine oxidase inhibitors); 2002 pumps were replaced w/ 2004 pumps after 2 weeks to complete a 6 week infusion; agents infused singly or concommitant in the same pump.

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3. Levetiracetam

16000 Ko, A. R., Kang, T. C. Blockade of endothelin B receptor improves the efficacy of levetiracetam in chronic epileptic rats. Seizure 2015; 31(--):133-40. >>> Levetiracetam; SB202190; BQ788; SC; Rat; 1003D; Controls received mp w/ vehicle; animal info (male, Sprague Dawley, 7 days); pumps replaced between trials;.

15004 Levesque, M., Behr, C., Avoli, M., Avoli, M. The anti-ictogenic effects of levetiracetam are mirrored by interictal spiking and high-frequency oscillation changes in a model of temporal lobe epilepsy. SEIZURE-EUROPEAN JOURNAL OF EPILEPSY 2015; 25(--):18-25. >>> Levetiracetam; Saline; SC; Rat; 2ML2; Controls received mp w/ vehicle; animal info (male, Sprague Dawley, 250-300g); cardiovascular;“These pumps deliver a continuous dosing over 2 weeks, circumventing the need for repetitive invasive blood sampling. ” pg 19;.

14948 Hall, A.M., Throesch, B.T., Buckingham, S.C., Markwardt, S.J., Peng, Y., Wang, Q., Hoffman, D.A., Roberson, E.D., Hoffman, D.A. Tau-Dependent Kv4.2 Depletion and Dendritic Hyperexcitability in a Mouse Model of Alzheimer's Disease. JOURNAL OF NEUROSCIENCE 2015; 35(--):6221-6230. >>> Levetiracetam; Saline; SC; Mice; 2004; Controls received mp w/ vehicle; animal info (hAPPJ20 on C57BL6J background); neurodegenerative (Alzheimer's disease); pumps primed at 37C for 24 hours;.

13446 Suberbielle, E., Sanchez, P.E., Kravitz, A.V., Wang, X., Ho, K., Eilertson, K., Devidze, N., Kreitzer, A.C., Mucke, L. Physiologic brain activity causes DNA double-strand breaks in neurons, with exacerbation by amyloid-beta. Nature Neuroscience 2013; 16(-5-):613-U140. >>> Levetiracetam; Saline; SC; Mice; Controls received mp w/ saline; animal info (4-5 months, heterozygous hAPP transgenic and wild-type, C57Nl/6J);.

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4. Phenobarbital

494 Hock, F.J., Beyhl, F.E. A novel method for the administration of the enzyme inducer phenobarbital to rats via an osmotic minipump. IRSC Med. Sci. : Biochem 1984; 12(-8-):661. >>> Phenobarbital; SC; rat; 2002; Comparison of phenobarb. consumed po in drinking water vs. mp infusion; author states advantages of mp use.

447 Davis, T.P., Schoemaker, H., Culling, A.J. Centrally acting drugs alter in vitro B-endorphin processing in the rat. Eur. J. Pharmacol 1984; 100(--):249-251. >>> Chlorpromazine; haloperidol; phenobarbital; promethazine; SC; Rat; 2001; Comparison of agents effects.

401 Kuhnz, W., Zierer, R., Nau, H. A new method for kinetic studies of drug interactions in experimental animals during steady state: controlled-rate application of valproic acid, phenobarbital and their combinations via implanted osmotic minipumps in the mouse. Arzneimittelforschung 1983; 33(-11-):1579-1582. >>> Phenobarbital, sodium; Valproate, sodium; Water; SC; mice (pregnant); 2001; 2002; no stress see p. 1580, 1582; 1-2 pumps/animal; VPA and PB used singly and in combination in mp.

311 Kapetanovic, I.M., Sweeney, D.J., Rapoport, S.I. Phenobarbital pharmacokinetics in rat as a function of age. Drug Metab. Disp 1982; 10(-6-):586-589. >>> Phenobarbital; Water; IP; rat; bolus injec. vs. mp infusion.

36 Tabakoff, B., Ritzmann, R.F., Oltmans, G.A. The effect of selective lesions of brain noradrenergic systems on the development of barbiturate tolerance in rats. Brain Research 1979; 176(--):327-336. >>> Phenobarbital, sodium; Propylene glycol; Water; CSF/CNS; rat; some groups given 6-OHDA or vehicle of ascorbic acid in Artificial CSF prior to infusion.

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5. Promethazine

447 Davis, T.P., Schoemaker, H., Culling, A.J. Centrally acting drugs alter in vitro B-endorphin processing in the rat. Eur. J. Pharmacol 1984; 100(--):249-251. >>> Chlorpromazine; haloperidol; phenobarbital; promethazine; SC; Rat; 2001; Comparison of agents effects.

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6. Tiagabine

4834 Cleton, A, Altorf, B.A, Voskuyl, R.A, Danhof, M. Pharmacokinetic-pharmacodynamic modelling of tiagabine CNS effects upon chronic treatment in rats: lack of change in concentration-EEG effect relationship.. European Journal of Pharmacology 2000; 12(--):141-150. >>> Tiagabine;; Saline;; IV (jugular);; rat;; 2ML2;; Controls received mp w/ vehicle; functionality of mp verified by plasma levels; dose-response (graph p. 145); comparison of IV injections vs. mp; Tiagabine is a GABA uptake inhibitor; seizure prevention; Epilepsy;.

3523 Halonen, T., Nissinen, J., Jansen, J.A., Pitkanen, A. Tiagabine prevents seizures, neuronal damage and memory impairment in experimental status epilepticus. Eur. J. Pharmacol 1996; 299(--):69-81. >>> Tiagabine; Propylene glycol; SC; rat; 2ML1; functionality of mp verified by in vitro testing and residual volumes; dose-response; half-life (p. 70); compound stable for one week (see p. 78); stability.

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7. Valproic

15698 Chang, C.Z., Wu, S.C., Lin, C.L., Kwan, A.L., Chang, C.Z. Valproic acid attenuates intercellular adhesion molecule-1 and E-selectin through a chemokine ligand 5 dependent mechanism and subarachnoid hemorrhage induced vasospasm in a rat model. Journal of Inflammation-London 2015; 12(--):U1-U11. >>> Valproic acid; PBS; Rat; Controls received mp w/ vehicle; animal info (male, Sprague Dalwey, 300-400g); dose-response (4); ischemia (cerebral); behavioral testing (modified limb-placing test); immunology;.

14872 Chang, C.Z., Wu, S.C., Lin, C.L., Kwan, A.L., Chang, C.Z. Valproic acid attenuates intercellular adhesion molecule-1 and E-selectin through a chemokine ligand 5 dependent mechanism and subarachnoid hemorrhage induced vasospasm in a rat model. Journal of Inflammation-London 2015; 12(--):U1-U11. >>> Valproic acid; PBS; Rat; Controls received mp w/ vehicle; animal info (male, Sprague Dawley, 300-400g); ischemia (cerebral); dose-response (pg 4-6); behavioral testing (modified limb-placing test); cardiovascular; bp measured using tail cuff;.

14841 Bates, R.C., Stith, B.J., Stevens, K.E., Bates, R.C. Increasing pro-survival factors within whole brain tissue of Sprague Dawley rats via intracerebral administration of modified valproic acid. JOURNAL OF PHARMACOLOGICAL SCIENCES 2015; 128(--):193-201. >>> Valproic acid-PEG; CSF/CNS (caudate putamen); CSF/CNS (sagittal fissure); Rat; 2004; Animal info (male, Sprague Dawley, 275-300g); ALZET brain infusion kit 1 used; behavioral testing (elevated plus maze, open field test); wound clips used;.

13325 Bates, R.C., Stith, B.J., Stevens, K.E. Chronic central administration of valproic acid: incrased pro-survival phospho-proteins and growth cone associated proteins with no behavioral pathology. Pharmacology Biochemistry and Behavior 2012; 103(--):237-244. >>> Valproic Acid; SC; Rat; 2004; Controls received mp w/ saline; animal info (Sprague-Dawley, adult male, 250-280g); ALZET brain infusion kit (1) used; behavioral testing (elevated plus maze, and open field maze).

9835 Kitazoe, K., Abe, M., Hiasa, M., Oda, A., Amou, H., Harada, T., Nakano, A., Takeuchi, K., Hashimoto, T., Ozaki, S., Matsumoto, T. Valproic acid exerts anti-tumor as well as anti-angiogenic effects on myeloma. International Journal of Hematology 2009; 89(-1-):45-57. >>> Valproic acid; PBS; SC; Mice (SCID); 2002; Controls received mp w/vehicle; cancer (myeloma); animal info (8-10 wks old, female).

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8. Valproic Acid

Q4357 Chang,C.Z., Wu,S.C., Lin,C.L., Kwan,A.L., Chang,C.Z. Valproic acid attenuates intercellular adhesion molecule-1 and E-selectin through a chemokine ligand 5 dependent mechanism and subarachnoid hemorrhage induced vasospasm in a rat model. Journal of Inflammation-London 2015; 12(--):U1-U11. >>> Valproic acid; PBS; Rat; 5 days; Controls received mp w/ vehicle; animal info (male, Sprague Dawley, 300-400g); ischemia (cerebral); dose-response (pg 4-6); behavioral testing (modified limb-placing test); cardiovascular; bp measured using tail cuff;.

Q4323 Bates,R.C., Stith,B.J., Stevens,K.E., Bates,R.C. Increasing pro-survival factors within whole brain tissue of Sprague Dawley rats via intracerebral administration of modified valproic acid. JOURNAL OF PHARMACOLOGICAL SCIENCES 2015; 128(--):193-201. >>> Valproic acid-PEG; CSF/CNS (caudate putamen); CSF/CNS (sagittal fissure); Rat; 2004; 25 days; Animal info (male, Sprague Dawley, 275-300g); ALZET brain infusion kit 1 used; behavioral testing (elevated plus maze, open field test); wound clips used;.

Q3024 Bates,R.C., Stith,B.J., Stevens,K.E. Chronic central administration of valproic acid: incrased pro-survival phospho-proteins and growth cone associated proteins with no behavioral pathology. Pharmacology Biochemistry and Behavior 2012; 103(--):237-244. >>> Valproic Acid; SC; Rat; 2004; 28 days; Controls received mp w/ saline; animal info (Sprague-Dawley, adult male, 250-280g); ALZET brain infusion kit (1) used; behavioral testing (elevated plus maze, and open field maze).

P9619 Kitazoe,K., Abe,M., Hiasa,M., Oda,A., Amou,H., Harada,T., Nakano,A., Takeuchi,K., Hashimoto,T., Ozaki,S., Matsumoto,T. Valproic acid exerts anti-tumor as well as anti-angiogenic effects on myeloma. International Journal of Hematology 2009; 89(-1-):45-57. >>> Valproic acid; PBS; SC; Mice (SCID); 2002; 14 days; Controls received mp w/vehicle; cancer (myeloma); animal info (8-10 wks old, female).

P9073 Shu,Q., Antalffy,B., Su,J.M., Adesina,A., Ou,C.N., Pietsch,T., Blaney,S.M., Lau,C.C., Li,X.N. Valproic Acid prolongs survival time of severe combined immunodeficient mice bearing intracerebellar orthotopic medulloblastoma xenografts. Clin.Cancer Res. 2006/8/1; 12(-15-):4687-4694. >>> Valproic acid; Sodium chloride; SC; Mice (SCID); 2001; 14 days; Controls received no treatment; pumps replaced after 7 days; animal info (6-10 wks old, Rag 2).

P8386 Serralta,A., Barcia,J.A., Ortiz,P., Duran,C., Hernandez,M.E., Alos,M. Effect of intracerebroventricular continuous infusion of valproic acid versus single i.p. and i.c.v. injections in the amygdala kindling epilepsy model. Epilepsy Research 2006; 70(-1-):15-26. >>> Valproic acid; Saline; CSF/CNS; Rat; 2001; 2002; 7 days; Controls received no treatment; dose-response (fig. 1); comparison of icv, IP injections vs. mp; no stress (see pg. 22); toxicology; multiple pumps per animal (2); animal info (male, Wistar, amygdala-kindled epilepsy, 380-420g.); mp primed 1 hr. in 37.5 celsius saline; evans blue dye used to confirm cannula placement, "chronic i.c.v. VPA infusion affords protection against kindled seizures accompanied by less ataxia and sedation" (pg. 24).

P3616 Ohdo,S., Ogawa,N., Nakano,S., Higuchi,S. Influence of feeding schedule on the chronopharmacological aspects of sodium valproate in mice. J.Pharmacol.Exp.Ther. 1996; 278(-1-):74-81. >>> Valproic acid; Saline, sterile physiological; SC; mice; 2001; no duration posted; functionality of mp verified by plasma levels; half-life of less than 1 hour (p. 76); 2 mps implanted concomitantly.

P2820 Song,J.-G. Chronopharmacokinetices of valproic acid in mice following contsant-rate administration by osmotic minipump. Chinese Pharmacological Bulletin 1995; 11(-2-):135-136. >>> Valproic acid; SC; mice; no duration posted; comparison of iv injections vs. mp; article in Chinese w/ abstract in English.

P1335 Paulson,R., Sucheston,M., Hayes,T., Weiss,H., Sachs,L., Oca,M., Kernan,B., Weiss,S. Effects of sodium valproate and oxygen on the CD-1 mouse fetus. J.Craniofac.Genet.Dev.Biol. 1988; 8(--):35-42. >>> Valproic acid; Sodium carbonate; Water; SC; mice (pregnant); 2001; 7 days; dose-response (text, graph); half-life; 2 pumps implanted simultaneously; functionality of mp verified by plasma levels; no stress; toxicology/teratology.

P0886 Loscher,W. Development of tolerance to the anticonvulsant effect of GABAmimetic drugs in genetically epilepsy-prone gerbils. Pharmacol.Biochem.Behav. 1986; 24(--):1007-1013. >>> Aminobutyric acid, Y-acetylenic Y-; Aminooxyacetic acid; Diazepam; THIP; Valproic acid; Saline; SC; rat; 2ML2; 2 weeks; controls received mp w/saline; diazepam too unstable to be used in mp; epilepsy; functionality of mp verified after 14 day exper. period - all 50 mps worked accurately; stability of VPA, THIP, GAG and AOAA.

P0848 Nau,H. Valproic acid teratogenicity in mice after various administration and phenobarbital-pretreatment regimens: the parent drug and not one of the metabolites assayed is implicated as teratogen. Fundam.Appl.Toxicol. 1986; 6(-4-):662-668. >>> Valproic acid; Water; SC; mice; 1 day; teratology; states pump rate at 8 ul/hr; 2 doses of vpa infused; comparison of SC or IP injections or oral dose vs. mp infusion.

P0366 Loscher,W., Nau,H. Distribution of valproic acid and its metabolites in various brain areas of dogs and rats after acute and prolonged treatment. J.Pharmacol.Exp.Ther. 1983; 226(-3-):845-854. >>> Valproic acid; SC; rat; 2ML2; 1, 3, or 14 days; no comment posted.

P0274 Nau,H., Zierer,R. Pharmacokinetics of valproic acid and metabolites in mouse plasma and brain following constant-rate application of the drug and its unsaturated metabolite with an osmotic delivery system. Biopharm.Drug Disp. 1982; 3(--):317-328. >>> Valproic acid; Sodium bicarbonate; Water; SC; mice; 2001; 2002; 1 week; intermittent sc. injec. vs. mp infusion; 1 or 2 pumps/animal; comparison of human vs. animal pharmacokinetics.

P0175 Nau,H., Zierer,R., Spielmann,H., Neubert,D., Gansau,Ch. A new model for embryotoxicity testing: teratogenicity and pharmacokinetics of valproic acid following constant-rate administration in the mouse using human therapeutic drug and metabolite concentrations. Life Sci. 1981; 29(-26-):2803-2813. >>> Valproic acid; Water; SC; mice; 2001; 7 days; 1 or 2 pumps/mouse; comparison of injection vs. infusion and human vs. animal pharmacokinetics.

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9. Vigabatrin

5015 Halonen, T., Nissinen, J., Pitkanen, A. Chronic elevation of brain GABA levels beginning two days after status epilepticus does not prevent epileptogenesis in rats. Neuropharmacology 2001; 40(--):536-550. >>> Vigabatrin; Saline; SC; rat; 2ML2; controls received mp w/ vehicle; long-term study, pumps replaced every 2 weeks for 10 weeks; epilepsy; seizures..

4445 Pitkanen, A., Nissinen, J., Jolkkonen, E., Tuunanen, J., Halonen, T. Effects of vigabatrin treatment on status epilepticus-induced neuronal damage and mossy fiber sprouting in the rat hippocampus. Epilepsy Research 1999; 33(--):67-85. >>> Vigabatrin;; Saline;; SC;; rat;; 2ML1;; controls received mp with vehicle; functionality of mp verified by plasma levels and residual volume; long-term study, pumps replaced every 2 weeks; enzyme inhibitor;.

4351 Golombek, D.A., Ralph, M.R. Inhibition of GABA transaminase enhances light-induced circadian phase delays but not advances. J. Biol. Rhythms 1994; 9(-3-4-):251-261. >>> Vigabatrin; Saline; IP; hamster; 2002; controls received mp w/saline or no treatment; comparison of injections vs. mp; GABA transaminase inhibitor.

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“Angiostatin was administered through continuous infusion...the continuous administration of angiogenesis inhibitors has greater therapeutic efficacy than the more commonly used twice-daily injections.” (p. 80) Reijneveld et al., European Journal of Clinical Investigation 2003;33:76-81.