References on the Administration of Cholinergic Agents Using
ALZET^® Osmotic Pumps

1. Acetylcholine

P6643 Reyes,A.E., Chacon,M.A., Dinamarca,M.C., Cerpa,W., Morgan,C., Inestrosa,N.C. Acetylcholinesterase-A beta complexes are more toxic than A beta fibrils in rat hippocampus - Effect on rat beta-amyloid aggregation, laminin expression, reactive astrocytosis, and neuronal cell loss. American Journal of Pathology 2004; 164(-6-):2163-2174. >>> Amyloid protein, beta (1-40); acetylcholinesterase; PBS; CSF/CNS (dorsal hippocampus); Rat; 2002; 4 weeks; 14 days; Comparison of acute injections vs. mp; brain tissue distribution; peptides.

P1926 Touvay,C., Pfister,A., Vilain,B., Carre,C., Page,C.P., Lellouch-Tubiana,A., Pignol,B., Mencia-Huerta,J.M., Braquet,P. Effect of long-term infusion of platelet-activating factor on pulmonary responsiveness and morphology in the guinea-pig. Pulmon.Pharm. 1991; 4(--):43-51. >>> Acetylcholine; Platelet activating factor; Albumin, bovine serum; Saline; IV (jugular); guinea-pig; 2002; 15 days; Cholinergic agent; stability verified by measuring biological activity of residual solution from pumps after 12 days, no loss of activity observed.

P0812 Shimazu,T., Noma,M., Saito,M. Chronic infusion of norepinephrine into the ventromedial hypothalmus induces obesity in rats. Brain Research 1986; 369(-1/2-):215-223. >>> Acetylcholine chloride; Cefalotin; Cholecystokinin tetrapeptide; Epinephrine HCl; Bombesin; Endorphin, B-; Enkephalin, methionine-; Norepinephrine HCl; Saline; Sodium bisulfite; CSF/CNS (hypothalamus); rat; 2002; 5-20 weeks; Cholinergic agent; pumps replaced periodically; mp connected to perm. steel cannula in hypothalamus; cannula fitted w/removable protector; (see p.217); agents infused sep. (cefalotin infused w/each agent); long-term study; peptides.

P0439 Costall,B., Domeney,A.M., Naylor,R.J. Locomotor hyperactivity caused by dopamine infusion into the nucleus accumbens of rat brain: specificity of action. Psychopharmacology 1984; 82(--):174-180. >>> Acetylcholine HCl; Aminobutyric acid, Y-; Serotonin bimaleinate; Dopamine HCl; Norepinephrine bitartrate; Nitrogen; Sodium metabisulfite; CSF/CNS (nucleus accumbens); rat; 2002; 13 days; Cholinergic agent; comparison of agents effects; no stress p. 175; stability of substances remaining in pump after 13 days was verified.

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2. Atropine

P5328 Basile,A.S., Fedorova,I., Zapata,A., Liu,X.G., Shippenberg,T., Duttaroy,A., Yamada,M., Wess,J. Deletion of the M-5 muscarinic acetylcholine receptor attenuates morphine reinforcement and withdrawal but not morphine analgesia. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES O F AMERICA 2002; 99(-17-):11452-11457. >>> Atropine sulfate; SC; Mice; 7 days; Muscarinic antagonist.

P5092 Dupont,E, Canu,M-H, Falempin,M. Atropine prevents the changes in the hindlimb cortical area induced by hypodynamia-hypokinesia. Brain Research 2002; 926(--):51-57. >>> Atropine sulfate; CSF, artificial; CSF/CNS (cortex); rat; 2002; 14 days; controls received mp w/ vehicle; brain tissue distribution; atropine is a muscarinic antagonist; agent infused topically to cortex, crosses blood-brain barrier to reach and be absorbed in primary somatosensory cortex; "We used an ALZET pump because (i) administration was continuous and constant and (ii) atropine was delivered onto the cortical surface." (p. 55).

P2824 Witt-Enderby,P.A., Yamamura,H.I., Halonen,M., Lai,J., Palmer,J.D., Bloom,J.W. Regulation of airway muscarinic cholinergic receptor subtypes by chronic anticholinergic treatment. Mol.Pharmacol. 1995; 47(--):485-490. >>> Atropine sulfate; SC; rabbit; 2ML4; 7, 14 or 27 days; controls received mp with vehicle; functionality of mp verified by taking blood plasma levels.

P2721 Lapchak,P.A., Araujo,D.M., Hefti,F. Cholinergic regulation of hippocampal brain-derived neurotrophic factor mRNA expression: evidence from lesion and chronic cholinergic drug treatment studies. Neuroscience 1993; 52(-3-):575-585. >>> Atropine sulfate; Nicotine bitartrate; rat; 2002; 14 days; controls received mp w/ saline or were unlesioned.

P2119 Wall,S.J., Yasuda,R.P., Li,M., Ciesla,W., Wolfe,B.B. Differential regulation of subtypes M1-M5 of muscarinic receptors in forebrain by chronic atropine administration. J.Pharmacol.Exp.Ther. 1992; 262(-2-):584-588. >>> Atropine; SC; rat; 2ML2; 14 days; no comment posted.

P3493 Ellis,J., Lenox,R.H. Chronic lithium treatment prevents atropine-induced supersensitivity of the muscarinic phosphoinositide response in rat hippocampus. Biol.Psychiatry 1990; 28(--):609-619. >>> Atropine sulfate; Saline; SC; rat; 6 days; controls received mp w/ saline.

P1751 Watson,G.E., Pearson,S.K., Falany,J.L., Culp,D.J., Tabak,L.A., Bowen,W.H. The effect of chronic atropine treatment on salivary composition and caries in rats. J.Dent.Res. 1989; 68(-12-):1739-1745. >>> Atropine; Saline; SC; rat; 2ML4; 24 days; functionality of mp verified by measuring blood levels; stability verified at 7 days in vitro.

P1359 Levin,R.M., Ruggieri,M.R., Lee,W., Wein,A.J. Effect of chronic atropine administration on the rat urinary bladder. J.Urol. 1988; 139(--):1347-1349. >>> Atropine; Saline; SC; rat; 2ML2; 1, 2, 4, 7, 11, 14 days and 6 hours; dose-response (text); functionality of mp verified by serum levels.

P0908 Frey,P. Changes in cholecystokinin content in rat brain after subchronic treatment with neuroleptics. Ann.N.Y.Acad.Sci. 1985; 448(--):601-603. >>> Flupenthixol, cis-; Flupenthixol, trans-; Amitriptyline; Amphetamine; Atropine; Chlorpromazine; Clozapine; Fluphenazine; Haloperidol; Morphine; Prazosin; SC; rat; 2 weeks; mp model not stated; comparison of sc injections vs. mp infusion; antihypertensive.

P0683 Pedigo Jr,N.W., Polk,D.M. Reduced muscarinic receptor plasticity in frontal cortex of aged rats after chronic administration of cholinergic drugs. Life Sci. 1985; 37(-15-):1443-1449. >>> Methylatropine; Oxotremorine; Saline; CSF/CNS; rat; 2ML4; 3 weeks; comparison of agents effects in young and old rats; stability of drugs at 37C determined at weekly intervals for 5 wks by bioassay; delivery into lateral cerebroventricle.

P0423 Wu,Y.Y., Wei,E.T. Mechanisms underlying the pressor responses to acute and chronic intraventricular administration of carbachol in the rat. J.Pharmacol.Exp.Ther. 1984; 228(-2-):354-363. >>> Atropine methyl nitrate; Hexamethonium bromide; Carbachol; Saline; CSF/CNS; SC; rat; 2001; 2002; 1-12 days; comparison of agents effects; pumps primed in saline before implant; carbachol admin. sc in one exp., other exp. deliv. Car., Hex.,&Atr. icv; antihypertensive.

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3. Bethanechol Chloride

S0642 Imamura,K., Kasamatsu,T. Noradrenergic and cholinergic interaction in ocular dominance plasticity. Society for Neuroscience Abstracts, 16th Annual Meeting, Nov.9-14, Washington, DC 1986; 12(--):1372-. >>> Bethanechol chloride; Dopamine, 6-hydroxy-; Propranolol; CSF/CNS (visual cortex); cat (kitten); 1 week; Cholinergic agent; controls received mp w/vehicle; mp connected to cannula in visual cortex.

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4. Carbachol

P0998 Shiromani,P.J., Fishbein,W. Continuous pontine cholinergic microinfusion via mini-pump induces sustained alterations in rapid eye movement (REM) sleep. Pharmacol.Biochem.Behav. 1986; 25(-6-):1253-1261. >>> Carbachol; Scopolamine; Saline; CSF/CNS; CSF/CNS (medulla); CSF/CNS (pons); rat; 2001; 7 days; Cholinergic agent; mp w/vehicle; mp connected to cann. in brain sites; MP failed to deliver drugs after 5 days possibly due to extended length of tubing.

P0628 Fitts,D.A., Thunhorst,R.L., Simpson,J.B. Fluid intake, distribution, and excretion during lateral ventricular infusions of carbachol in rats. Brain Research 1985; 332(--):237-245. >>> Carbachol; Saline; CSF/CNS; rat; 2001; 6 days; comparison of icv injec. (acute infusion) vs. mp infusion; stability of residual carbachol verified by dipsogenic effect on 2 bioassay rats.

P0199 Wu,Y.Y., Wei,E.T. Infusions of chemicals into the brain and the development of sustained elevations of blood pressure in the rat. Life Sci. 1982; 30(--):1537-1545. >>> Carbachol chloride; Echothiophate iodide; Histamine dihydrochloride; Prostaglandin E2; Thyrotropin-rel. factor; Saline; CSF/CNS; rat; 1701; 2001; no duration posted; 2001 w/carbachol&echothiophate, 1701 w/histamine, PGE2,&TRH, 7 days; comparison of agents effects.

P0056 Avrith,D.B., Fitzsimons,J.T. Increased sodium appetite in the rat induced by intracranial administration of components of the renin-angiotensin system. J.Physiol. 1980; 301(--):349-364. >>> Carbachol; Saline; CSF/CNS; rat; no duration posted; Sage pump also used; comparison of injection vs. infusion.

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5. Oxotremorine

P1408 Miyamoto,M., Narumi,S., Nagaoka,A., Coyle,J.T. Effects of continuous infusion of cholinergic drugs on memory impairment in rats with basal forebrain lesions. J.Pharmacol.Exp.Ther. 1989; 248(-2-):825-835. >>> Oxotremorine; Physostigmine sulfate; Saline; SC; rat; 2002; 3 weeks; no comment posted.

P0663 Fernando,J.C.R., Hoskins,B., Ho,I.K. Rapid induction of supersensitivity to muscarinic antagonists-induced motor excitation by continuous stimulation of cholinergic receptors. Life Sci. 1985; 37(-9-):883-892. >>> Oxotremorine; Physostigmine sulfate; Saline; SC; rat; 2002; 2 weeks; comparison of single sc injec vs. daily injec vs. mp infusion of agents effects.

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6. Physostigmine

P7570 Philippens,I.H.C.H., Joosen,M.J.A., Vanwersch,R.A.P. Stress adversely affects efficacy of physostigmine-scopolamine pretreatment against soman in guinea pigs. Pharmacology Biochemistry and Behavior 2005; 82(-1-):125-132. >>> Physostigmine; scopolamine bromide; Water, distilled; propylene glycol; acetic acid, glacial; ethanol; SC; Guinea-pig; 2002; 2 weeks; Controls received mp w/ vehicle; post op. care (nobecutane); animal info (male, dunkin-hartley albino, 400-450 g); 10% ETOH.

P6802 Choi,E.K., Park,D., Yon,J.M., Hur,G.H., Ha,Y.C., Che,J.H., Kim,J., Shin,S., Jang,J.Y., Hwang,S.Y., Seong,Y.H., Kim,D.J., Kim,J.C., Kim,Y.B. Protection by sustained release of physostigmine and procyclidine of soman poisoning in rats. European Journal of Pharmacology 2004; 505(-1-3-):83-91. >>> Physostigmine salicytate; procyclidine hydrochloride; Propylene glycol; acetic acid, glacial; ethanol; water; SC; Rat; 2001; 3 days; Functionality of mp verified by plasma levels; dose-response (table 1); enzyme inhibitor (cholinesterase); procyclidine is an NMDA antagonist.

P6417 Langley,R.J., Kalra,R., Mishra,N.C., Sopori,M.L. Central but not the peripheral action of cholinergic compounds suppresses the immune system. Journal of Neuroimmunology 2004; 148(-1-2-):140-145. >>> Physostigmine; pyridostigmine bromide; edrophonium; Saline; CSF, artificial; SC; CSF/CNS; Rat; 2ML4; 3 weeks; Controls received mp w/ vehicle; enzyme inhibitor (acetylcholinesterase); immunology; ALZET brain infusion kit.

P5707 Muggleton,N.G., Bowditch,A.P., Crofts,H.S., Scott,E.A.M., Pearce,P.C. Assessment of a combination of physostigmine and scopolamine as pretreatment against the behavioral effects of organophosphates in the common marmoset (Callithrix jacchus). Psychopharmacology 2003; 166(-3-):212-220. >>> Physostigmine salicylate; scopolamine hydrobromide; Saline; SC; Monkey (marmoset); 2002; 14 days; Controls received mp w/ vehicle; behavioral testing; agents infused via same pumps; toxicology.

P5352 Wetherell,J., Hall,T., Passingham,S. Physostigmine and hyoscine improves protection against the lethal and incapacitating effects of nerve agent poisoning in the guinea-pig. Neurotoxicology 2002; 23(-3-):341-349. >>> Physostigmine salicylate; Hyoscine hydrobromide; Pyridostigmine; Saline; SC; Guinea-pig; 2001; 7 days; Physostigmine and hyoscine infused together; toxicology.

P5145 Meshulam,Y., Cohen,G., Chapman,S., Alkalai,D., Levy,A. Prophylaxis against organophosphate poisoning by sustained release of scopolamine and physostigmine. Journal of Applied Toxicology 2001; 21(--):S75-S78. >>> Scopolamine; Physostigmine; Propylene glycol; Ethanol; Water; Acetic acid, glacial; SC; DOG; 2001; 24 or 48 hours; functionality of mp verified by plasma scopolamine&physostigmine levels; dose-response (table, p. S77); toxicology; vehicle was 10% ethanol, 20% PG, 70% water, 0.0035% AA; mentions benefits of infusion via pump (p. S77).

P4935 Beach,T.G., Kuo,Y.M., Schwab,C., Walker,D.G., Roher,A.E. Reduction of cortical amyloid beta levels in guinea pig brain after systemic administration of physostigmine. Neuroscience Letters 2001; 310(--):21-24. >>> Physostigmine salicylate; Saline, sterile; SC; guinea-pig; 2ML2; 10 days; controls received mp w/ vehicle; peptides; neurodegenerative (Alzheimer's disease); peptide amyloid beta; physostigmine is an acetylcholesterase enzyme inhibitor;.

P4925 Daniel,J.M., Dohanich,G.P. Acetylcholine mediates the estrogen-induced increase in NMDA receptor binding in CA1 of the hippocampus and the associated improvement in working memory. Journal of Neuroscience 2001; 21(-17-):6949-6956. >>> Pyridostigmine; Huperzine; Physostigmine; Scopolamine;; SC;; guinea-pig;; 3 days; Controls received sham operation; enzyme inhibitor; these are poisons known to be acetylcholinesterase inhibitors; doses inhibited 30% of AChE activity; Physostigmine was infused alone or together with Scopolamine; toxicology.

P4230 Philippens,I.H.C.H.M., Busker,R.W., Wolthuis,O.L., Olivier,B., Bruijnzeel,P.L.B., Melchers,B.P.C. Subchronic physostigmine pretreatment in guinea pigs: effective against soman and without side effects. Pharmacol.Biochem.Behav. 1998; 59(-4-):1061-1067. >>> Physostigmine; Scopolamine; Propylene glycol; Ethanol; Water; SC; guinea-pig; 2002; 2 weeks; controls received mp w/vehicle; functionality of mp verified by scopolamine plasma levels; agents infused alone or combined in same pump; "because a bolus injection of physostigmine is not a very realistic pretreatment procedure, a more chronic application was considered and evaluated" (p. 1062).

P4427 Meshulam,Y, Davidovici,R, Wengier,A, Levy,A. Prophylactic transdermal treatment with Physostigmine and Scopolamine against soman intoxication in guinea-pigs.. Journal of Applied Toxicology 1995; 15(--):263-266. >>> Physostigmine;; SC;; guinea-pig;; 2001;; ; comparison of acute injections vs. mp; half-life (p. 263); "Physostigmine concentrations needed for protection under continuous delivery were significantly smaller...than those needed following acute injection" (p. 265); Physostigmine has half life of 15 min. in rats and 30 min. in humans..

P2872 Wetherell,J.R. Continuous administration of low dose rates of physostigmine and hyoscine to guinea-pigs prevents the toxicity and reduces the incapacitation produced by soman poisoning. J.Pharm.Pharmacol. 1994; 46(--):1023-1028. >>> Physostigmine; Hyoscine; Saline, sterile; SC; guinea-pig; 2001; 2002; 1, 6 or 13 days; controls received sham surgery.

P2613 Meshulam,Y., Davidovici,R., Levy,A. Protection against soman and sarin exposure by transdermal physostigmine and scopolamine. Proc.Med.Def.Biosci.Rev. 1993; 2(--):812-819. >>> Physostigmine; SC; guinea-pig; 2001; 24 hours; comparison of transdermal administration vs. mp; toxicology; physostigmine administered w/ and w/out scopolamine.

P2363 Miller,S.A., Blick,D.W., Kerenyi,S.Z., Murphy,M.R. Efficacy of physostigmine as a pretreatment for organophosphate poisoning. Pharmacol.Biochem.Behav. 1993; 44(--):343-347. >>> Physostigmine salicylate; Propylene glycol; Acetic acid, glacial; Ethanol, absolute; Water; SC; rat; 2001; 3,4,5,6,7 days; controls received mp w/ vehicle solution; functionality of mp verified by ChE inhibition (graph, p. 345).

P2593 Anderson,D.R., Harris,L.W., Lennox,W.J., Solana,R.P. Effects of subacute pretreatment with carbamate together with acute adjunct pretreatment against nerve agent exposure. Drug Chem.Toxicol. 1991; 14(-1&2-):1-19. >>> Physostigmine salicylate; Pyridostigmine bromide; Acetic acid, glacial; Water; guinea-pig; 2ML2; 14 days; controls received mp w/ vehicle; functionality of mp verified by AChE assay; comparison of acute injections vs. mp; acute scopolamine administered concomitantly; toxicology.

P1891 Alberch,J., Carman-Krzan,M., Fabrazzo,M., Wise,B.C. Chronic treatment with scopolamine and physostigmine changes nerve growth factor (NGF) receptor density and NGF content in rat brain. Brain Research 1991; 542(--):233-240. >>> Physostigmine; SC; rat; 2001; 3, 7 days; no comment posted.

P1615 Mandel,R.J., Chen,A.D., Connor,D.J., Thal,L.J. Continuous physostigmine infusion in rats with excitotoxic lesions of the nucleus basalis magnocellularis: effects on performance in the water maze task and cortical cholinergic markers. J.Pharmacol.Exp.Ther. 1989; 251(-2-):612-619. >>> Physostigmine hemisulfate; Ethanol; Propylene glycol; Water; SC; rat; 1 week, 16 days; pump replaced at 12 days.

P1509 Lim,D.K., Ito,Y., Yu,Z.J., Hoskins,B., Ho,I.K. Prevention of soman toxicity after the continuous administration of physostigmine. Pharmacol.Biochem.Behav. 1989; 31(--):633-639. >>> Physostigmine salicylate; Ethanol; Acetic acid, glacial; Propylene glycol; Water; SC; guinea-pig; 2001; 4, 7 days; no comment posted.

P1508 Lim,D.K., Ito,Y., Stewart,T., Hoskins,B., Ho,I.K. Toxicity study of continuous administration of physostigmine salicylate. Pharmacol.Biochem.Behav. 1989; 31(--):627-631. >>> Physostigmine salicylate; Alcohol; Propylene glycol; Water; SC; guinea-pig; 2001; 7 days; stability of agent in vehicle tested.

P1483 Harris,L.W., Anderson,D.R., Lennox,W.J., Solana,R.P. Effects of subacute administration of physostigmine on blood acetylcholinesterase activity, motor performance, and soman intoxication. Toxicol.Appl.Pharmacol. 1989; 97(--):267-271. >>> Physostigmine salicylate; Acetic acid, glacial; Ethanol; Propylene glycol; Water; SC; rat; 2ML4; 28 days; functionality of mp verified in vitro.

P0978 James,M.K., Cubeddu,L.X. Pharmacologic characterization and functional role of muscarinic autoreceptors in the rabbit striatum. J.Pharmacol.Exp.Ther. 1987; 240(-1-):203-215. >>> Physostigmine; SC; rabbit; 2ML2; 14 days; controls received sham surgery; 2 doses of agent infused.

P0429 Girgis,M. A combined histochemical-neurophysiological technique for investigating the extent of diffusion of intracerebrally injected drugs. Acta Anat. 1983; 117(--):248-256. >>> Physostigmine; Reserpine; CSF/CNS (limbic system); cat; guinea-pig; monkey; rabbit; 3, 5, and 7 days; comparison of injec by microsyringe vs. mp infusion, infused hippocampus, septum, hypothalamus, caudate-putamen; chemitrode, mp advant. for icv admin; confusing paper; antihypertensive.

P0365 Loullis,C.C., Dean,R.L., Lippa,A.S., Meyerson,L.R., Beer,B., Bartus,R.T. Chronic administration of cholinergic agents: effects on behavior and calmodulin. Pharmacol.Biochem.Behav. 1983; 18(-4-):601-604. >>> Physostigmine; Scopolamine; Saline; SC; rat; 15 days; comparison of agents effects.

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7. Pyridostigmine

P8259 Dubovicky,M., Paton,S., Morris,M., Mach,M., Lucot,J.B. Effects of combined exposure to pyridostigmine bromide and shaker stress on acoustic startle response, pre-pulse inhibition and open field behavior in mice. Journal of Applied Toxicology 2007; 27(-3-):276-283. >>> Pyridostigmine bromide; SC; Mice; 1007D; 7 days; Controls received mp w/ vehicle, or isotonic saline; no stress (see pg. 278, 280); enzyme inhibitor (acetylcholinesterase); animal info (male, C57BL/6J, 24-26g., 2 months old).

P8345 Bernatova,I., Babal,P., Grubbs,R.D., Morris,M. Acetylcholinesterase inhibition affects cardiovascular structure in mice. PHYSIOLOGICAL RESEARCH 2006; 55(--):S89-S97. >>> Pyridostigmine bromide; SC; Mice; 1007D; 7 days; Controls received mp w/ isotonic saline; enzyme inhibitor (acetylcholinesterase); cardiovascular; animal info (male, C57BL/6J, 10-12 weeks old, 25 grams).

P8143 Griffiths,G.D., Hornby,R.J., Jagger,C.P., Brown,A.P., Stoten,A., Pearce,P.C., Scott,L., Pritchard,D.I. Development of methods to measure humoral immune responses against selected antigens in the common marmoset (Callithrix jacchus) and the effect of pyridostigmine bromide administration. INTERNATIONAL IMMUNOPHARMACOLOGY 2006; 6(-12-):1755-1764. >>> Pyridostigmine bromide; Saline, sterile isotonic; SC; Marmoset; 28 days; Controls received mp w/ vehicle; no stress (see p.1759,1762); immunology; animal info (male, female, 300-500g.); mp primed 40 hours; "delivery by pump ensured the animals would receive an appropriate dose of the drug over the desired time period.", oral delivery "would introduce unacceptable stress into the experiment and presentation in food was discounted because of difficulties in estimating the dose administered." (p.1757).

P8082 Hornby,R.J., Pearce,P.C., Bowditch,A.P., Scott,L., Griffiths,G.D. Multiple vaccine and pyridostigmine bromide interactions in the common marmoset Callithrix jacchus: Immunological and endocrinological effects. INTERNATIONAL IMMUNOPHARMACOLOGY 2006; 6(-12-):1765-1779. >>> Pyridostigmine bromide; Saline, sterile isotonic; SC; Marmoset; 2004; 28 days; Controls received mp w/ vehicle; no stress (see p.1776); immunology; animal info (female, vasectomized male, 331-565g. 2-5.5 yrs. old); mp primed 40 hours.

P7217 Griffiths,G.D., Telford,G., Hooi,D.S.W., Cook,D.L., Wilkinson,L.J., Green,C.A., Pritchard,D.I. A T-cell-dependent humoral immune response is preserved during the administration of the nerve agent pre-treatment pyridostigmine bromide in a murine model. INTERNATIONAL IMMUNOPHARMACOLOGY 2005; 5(-3-):525-540. >>> Pyridostigmine bromide; Saline, sterile isotonic; SC; Mice; 2004; 28 days; Controls received mp w/ vehicle; enzyme inhibitor (cholinesterase); immunology; mp primed in saline at 37 degrees celsius for 48 hours; "PB administration was achieved by 28-day mini-osmotic pumps thus removing the requirement for multiple oral dosing and the associated stress this may have caused." (p. 536).

P7030 Joaquim,L.F., Farah,V.M., Bernatova,I., Fazan,R.Jr, Grubbs,R., Morris,M. Enhanced heart rate variability and baroreflex index after stress and cholinesterase inhibition in mice. American Journal of Physiology-Heart and Circulatory Physiology 2004; 287(-1-):H251-H257. >>> Pyridostigmine; SC; Mice; 1007D; 3 days; Controls received mp w/ saline; enzyme inhibitor (acetylcholinesterase); cardiovascular.

P6741 Van Helden,H.P.M., Vanwersch,R.A.P., Kuijpers,W.C., Trap,H.C., Philippens,I.H.C., Benschop,H.P. Low levels of Sarin affect the EEG in marmoset monkeys: a pilot study. Journal of Applied Toxicology 2004; 24(-6-):475-483. >>> Pyridostigmine bromide; Propylene glycol: ethanol; acidic acid, glacial; water, distilled; SC; Marmoset; 2002; ; Controls received mp w/ vehicle; toxicology; sarin vapor.

P6551 Van Helden,H.P.M., Trap,H.C., Kuijpers,W.C., Oostdijk,J.P., Benschop,H.P., Langenberg,J.P. Low-level exposure of guinea pigs and marmosets to sarin vapour in air: Lowest-observable-adverse-effect level (LOAEL) for miosis. Journal of Applied Toxicology 2004; 24(-1-):59-68. >>> Pyridostigmine bromide; Propylene glycol; ethanol; water; acetic acid, glacial; SC; Guinea-pig; marmoset; 2002; 4 days; Controls received mp w/ vehicle; toxicology.

P5638 Bernatova,I., Dubovicky,M., Price,W.A., Grubbs,R.D., Lucot,J.B., Morris,M. Effect of chronic pyridostigmine bromide treatment on cardiovascular and behavioral parameters in mice. Pharmacology Biochemistry and Behavior 2003; 74(-4-):901-907. >>> Pyridostigmine bromide; Saline; SC; Mice; 1007D; 7 days; Controls received mp w/ vehicle; pyridostigmine blood levels checked; enzyme inhibitor (acetylcholinesterase)..

P5528 Lallement,G., Demoncheaux,J.P., Foquin,A., Baubichon,D., Galonnier,M., Clarencon,D., Dorandeu,F. Subchronic administration of pyridostigmine or huperzine to primates: Compared efficacy against soman toxicity. Drug and Chemical Toxicology 2002; 25(-3-):309-320. >>> Pyridostigmine; huperzine; SC; Monkey; 2ML1; 6 days; Enzyme inhibitor (acetylcholinesterase); toxicology.

P4817 Griffiths,G.D., Hornby,R.J., Stevens,D.J., Scott,L.A.M., Upshall,D.G. Biological consequences of multiple vaccine and pyridostigmine pretreatment in the guinea pig.. Journal of Applied Toxicology 2001; 21(--):59-68. >>> Pyridostigmine bromide;; Saline;; SC;; guinea-pig;; 28 days;; Controls received mp w/ vehicle; functionality of mp verified by AChE levels via assay p. 60; immunology; enzyme inhibitor; PB is an acetylcholinesterase inhibitor; toxicology.

P4806 Lallement,G., Foquin,A., Dorandeu,F., Baubichon,D., Carpentier,P. Subchronic administration of various pretreatments of nerve agent poisoning. II. Compared efficacy against soman toxicity. Drug and Chemical Toxicology 2001; 24(-2-):165-180. >>> Pyridostigmine; Huperzine; Physostigmine; Scopolamine;; SC;; guinea-pig;; 6 days;; Controls received sham operation; enzyme inhibitor; these are poisons known to be acetylcholinesterase inhibitors; doses inhibited 30% of AChE activity; Physostigmine was infused alone or together with Scopolamine; toxicology.

P3276 Matthew,C.B., Glenn,J.F., Bowers Jr,W.D., Navara,D.K. Cholinergic drug interactions and heat tolerance. Life Sci. 1994; 54(-17-):1237-1245. >>> Pyridostigmine bromide; SC; rat; 2ML2; 2 weeks; controls received mp w/saline; comparison of iv injection vs. mp; toxicology.

P3020 Walday,P., Aas,P., Haider,T., Fonnum,F. Effect of pyridostigmine pretreatment, HI-6 and toxogonin treatment on rat tracheal smooth muscle response to cholinergic stimulation after organophosphorus inhalation exposure. Arch.Toxicol. 1993; 67(--):212-219. >>> Pyridostigmine; SC; rat; 2001; 18 days; toxicology.

P2331 Koplovitz,I., Gresham,V.C., Dochterman,L.W., Kaminskis,A., Stewart,J.R. Evaluation of the toxicity, pathology, and treatment of cyclohexylmethylphosphonofluoridate (CMPF) poisoning in rhesus monkeys. Arch.Toxicol. 1992; 66(-9-):622-628. >>> Pyridostigmine; Saline; monkey; 2ML2; 3-12 days; no comment posted.

P1982 Adler,M., Deshpande,S.S., Foster,R.E., Maxwell,D.M., Albuquerque,E.X. Effects of subacute pyridostigmine administration on mammalian skeletal muscle function. J.Applied Toxicol. 1992; 12(-1-):25-33. >>> Pyridostigmine bromide; Citric acid; Sodium hydroxide; Parabens; Sodium citrate; SC; rat; 2ML2; 14 days; cholinesterase inhibitor.

P2303 Blick,D.W., Kerenyi,S.Z., Miller,S., Murphy,M.R., Brown,G.C., Hartgraves,S.L. Behavioral toxicity of anticholinesterases in primates: chronic pyridostigmine and soman interactions. Pharmacol.Biochem.Behav. 1991; 38(--):527-532. >>> Pyridostigmine bromide; Acetic acid; Sodium hydroxide; SC; monkey; 2ML1; 5 days; controls received mp w/ vehicle.

P2573 Kerenyi,S.Z., Murphy,M.R., Hartgraves,S.L. Toxic interactions between repeated soman and chronic pyridostigmine in rodents. Pharmacol.Biochem.Behav. 1990; 37(-2-):267-271. >>> Pyridostigmine bromide; Acetic acid; Sodium hydroxide; SC; rat; 2001; 7 days; controls received mp w/ vehicle; dose-response (p.268); toxicology.

P1109 Kerenyi,S.Z., Hartgraves,S.L. Premature excess release from the alzet osmotic pump. Pharmacol.Biochem.Behav. 1987; 27(-1-):199-201. >>> Dye, FD&C Red No. 40; Pyridostigmine; Acetate, sodium; Acetic acid; SC; rat; 2001; no duration posted; dose-response; mp malfunction; pyridostigmine used in vivo, dye in vitro; excessive early release of mp attributed to temp. change after implant.; stress/adverse reaction (cholinesterase poisoning due to mp malf.).

P0847 Hudson,C.S., Foster,R.E., Kahng,M.W. Ultrastructural effects of pyridostigmine on neuromuscular junctions in rat diaphragm. Neurotoxicology 1987; 7(-1-):167-186. >>> Pyridostigmine bromide; Citric acid monohydrate; Methyl paraben; Propyl paraben; Saline; Sodium citrate dihydrate; Water; SC; rat; 2ML2; 2, 7, 14 days; controls received mp w/vehicle; toxicology; various doses of agent infused; possible malfunction of one mp; comparison of sc injections vs. mp infusion; functionality of mp verified via assay.

P1085 Anderson,R.J., Chamberlain,W.L., Roesner,M., Dacko,C., Robertson,D.G. Decreased tetanic contracture of rat skeletal muscle induced by pyridostigmine. J.Toxicol.Environ.Health 1986; 18(--):221-230. >>> Pyridostigmine; Saline; rat; 1, 4, 10, 20 days; mp model not stated; controls received mp w/vehicle; 2 doses of agent infused; comparison of ip inject. vs. mp infusion; mp malfunction - residual drug in exiting tube gave equivalent of bolus injection but was corrected in later exp..

P0984 Shiloff,J.D., Clement,J.G. Effects of subchronic pyridostigmine pretreatment on the toxicity of soman. Can.J.Physiol.Pharmacol. 1986; 64(--):1047-1049. >>> Pyridostigmine; SC; rat; 2001; 5 days; 2001, 5 days; toxicology; teratology.

P0822 Hudson,C.S., Foster,R.E., Kahng,M.W. Neuromuscular toxicity of pyridostigmine bromide in the diaphragm, extensor digitorum longus, and soleus muscles of the rat. Fundam.Appl.Toxicol. 1985; 5(-6 pt. 2-):S260-S26S. >>> Pyridostigmine bromide; Citric acid monohydrate; Methyl paraben; Propyl paraben; Saline; Sodium citrate dihydrate; Water; SC; rat; 2ML2; 2 days; comparison of single injection vs. mp infusion; controls received mp w/ vehicle; study to determine neuromuscular effects of agent on different types of muscle fibers; toxicology.

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8. Scopolamine

P8200 Kotani,S., Yamauchi,T., Teramoto,T., Ogura,H. Pharmacological evidence of cholinergic involvement in adult hippocampal neurogenesis in rats. Neuroscience 2006; 142(-2-):505-514. >>> Scopolamine; Water, distilled; SC; Rat; 2ML4; 4 weeks; Controls received mp w/ vehicle; dose-response (fig.6); animal info (male, Sprague-Dawley, 200-250g., 5wks old).

P7514 West,C.H.K., Weiss,J.M. A selective test for antidepressant treatments using rats bred for stress-induced reduction of motor activity in the swim test. Psychopharmacology 2005; 182(-1-):9-23. >>> Amitriptyline HCl; venlafaxine HCl; clordiazepoxide HCl; imipramine HCl; phenelzine sulfate; scopolamine HBr; desipramine HCl; bupropion HCl; chlorpheniramine maleate; fluoxetine HCl; sertraline; amphetamine sulfate, D-; Water, sterile distilled; PEG; SC; Rat; 2ML2; 6,14 days; Controls received mp w/ vehicle; functionality of mp verified by agent blood levels; dose-response (fig. 5); animal info (male, female, susceptible, selectively bred); some animals had saline-filled catheter attached to mp to delay drug infusion by 5 days; "The most notable advantage of minipump delivery is that it eliminates stress resulting from daily injection of drug....minipumps also provide constant infusion of drug" (pg. 22).

P7259 Pereira,H.A.A., Benassi,T.K., Mello,T.E. Plastic changes and disease-modifying effects of scopolamine in the pilocarpine model of epilepsy in rats. Epilepsia 2005; 46(--):118-124. >>> Scopolamine hydrobromide; Saline, sterile; SC; Rat; 2002; 14 days; Controls received mp w/ vehicle, or no treatment; dose-response no stress (see pg. 120); epilepsy.

P5145 Meshulam,Y., Cohen,G., Chapman,S., Alkalai,D., Levy,A. Prophylaxis against organophosphate poisoning by sustained release of scopolamine and physostigmine. Journal of Applied Toxicology 2001; 21(--):S75-S78. >>> Scopolamine; Physostigmine; Propylene glycol; Ethanol; Water; Acetic acid, glacial; SC; Dog; 2001; 24 or 48 hours; functionality of mp verified by plasma scopolamine&physostigmine levels; dose-response (table, p. S77); toxicology; vehicle was 10% ethanol, 20% PG, 70% water, 0.0035% AA; mentions benefits of infusion via pump (p. S77).

P3550 Gordon,C.J. Pharmacological analysis of diisopropyl fluorophosphate: effects on core temperature, heart rate, and motor activity in the unrestrained rat. Pharmacol.Biochem.Behav. 1996; 55(-2-):185-194. >>> Scopolamine; Methylscopolamine nitrate; Salicylate, sodium; SC; rat; 2002; 10 days; temperatures were taken with radiotelemetry.

P3426 Macedoni-Luksic,M., Sket,D. Scopolamine modulates the effects of continuous amphetamine in rats. Acta Pharm. 1996; 46(--):23-30. >>> Amphetamine sulfate, d-; Scopolamine hydrobromide; Saline; SC; rat; 2ML1; 7 days; controls received mp w/ saline; functionality of mp verified by residual volume; tolerance.

P4255 Gu,Q., Singer,W. Effects of intracortical infusion of anticholinergic drugs on neuronal plasticity in kitten striate cortex. Eur.J.Neurosci. 1993; 5(--):475-485. >>> Scopolamine; Hexamethonium; Mecamylamine; Pirenzepine; Gallamine; Saline, sterile; CSF/CNS (visual cortex); cat (kitten); 2001; 8 days; controls received mp w/vehicle; stress/adverse reaction (p. 480); multiple pumps per animal (2) (one pump with drug, one pump with saline); agents infused separately or together in same pump; "necrosis develops around the tip of the cannulae" (p. 480).

P1021 Loiselle,J., Larose,L., Morisset,J. Contraindication for osmotic mini-pump in the abdominal cavity to study muscarinic cholinergic control of pancreatic enzyme secretion and muscarinic receptors. Int.J.Pancreatology 1986; 1(-3/4-):249-258. >>> Scopolamine, N-methyl; Saline; IP; SC; rat; 2002; 2 weeks; controls received mp w/vehicle or sham operation; animals received mp either sc or ip.

P0678 Morisset,J., Loiselle,J. Alteration of the rat exocrine pancreas after chronic scopolamine administration. Pharmacology 1985; 30(-6-):308-313. >>> Scopolamine, N-methyl; Saline; IP; rat; 2002; 2 weeks; comparison of single daily ip injec vs. mp infusion; advantage of mp model to study pancreatic receptor modulation p. 312.

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

1. Acetylcholine

2. Atropine

3. Bethanechol Chloride

4. Carbachol

5. Oxotremorine

6. Physostigmine

7. Pyridostigmine

8. Scopolamine

Sterile Catheter Tubing for Infusion Studies

References on the Administration of Cholinergic Agents Using
ALZET^® Osmotic Pumps