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8 Douglas, W.W. (1980): Histamine and 5-hydroxytryptamine (serotonin) and their antagonists. In: Goodman and Gilman s The Pharmacological Basis of Therapeutics, 6th Edition, A. Goodman Gilman, L.S. Goodman, T.W. Rail and F. Murad, ed. Macmillan Publishing Company, New York. Chapter 26, pp Humphrey, PPA et al. (1991): Preclinical studies on the anti-migraine drug, sumatriptan. Eur. Neurol, 31,
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14 Crampton et al. (1977): Long-term studies on chemically induced liver enlargement in the rat. Toxicology, 7, Schulte-Hermann, R. (1974): Induction of liver growth by xenobiotic compounds and other stimuli. CRC Crit. Rev. Toxicol., 3, Comer, C.P., et al. (1985): Changes in thyroidal function and liver UDP glucuronosyl transferase activity in rats following administraion of a novel imidazole (SC-37211), Toxicol. Appl. Pharmacol., 80, McClain, R.M. (1989): The significance of hepatic microsomal enzyme induction and altered thyroid function in rats: implications for thyroid gland neoplasia, Toxicol. Pathol., 17, Davies, D.T. (1993): Assessment of rodent thyroid endocrinology: Advantages and Pit-Falls, Comp. Hematol. Int., 3, AMERGE Tablets (naratriptan hydrochloride) In: Physician s Desk Reference, 53 rd ed., , ZOMIG Tablets (zolmitriptan) In: Physician s Desk Reference, 53 rd ed., , 1999.
15 30 T3 nmol/l T4 nmol/l TSH ng/ml t1/2, β phase hours ml/h/kg mg/kg 0.9 * 43.6 *** 8.9 * *** *** mg/kg *** 13.4 * a) *** *** Student t *: p=0.05, ***: p= mg/kg 300 mg/kg (g) (g) (g/100g BW) (g) (g/100g BW) mg/kg 300 mg/kg 0/5 0/5 0/5 4/5 0/5 1/5 0/5 4/ mg a) a) TSH, µiu /ml 1.32± ± ± ± ± ± ± ±0.41 T3, pg/ml 3.0± ± ± ± ± ± ± ±0.4 T4, pg/ml 12.5± ± ± ± ± ± ± ±
16 Moro, F. et al. (1981): Serotonin nerve endings and regulation of pupillary diameter, Ann. Ophthalmol. 13, Douglas, W.W. (1980): Histamine and 5-hydroxytryptamine (serotonin) and their antagonists. In: Goodman and Gilman s The Pharmacological Basis of Therapeutics, 6th Edition, A. Goodman Gilman, L.S. Goodman, T.W. Rail and F. Murad, ed. Macmillan Publishing Company, New York. Chapter 26, pp Humphrey, PPA et al. (1991): Preclinical studies on the anti-migraine drug, sumatriptan. Eur. Neurol, 31, IMITREX Injection (sumatriptan succinate) In: Physicians Desk Reference, 53rd ed., , 1999 Owen, K. et al. (1995): The preclinical toxicological evaluation of sumatriptan, Human Exp. Toxicol., 14,
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26 11 AMERGE Tablets (naratriptan hydrochloride) In: Physicians Desk Reference, 53rd ed., , 1999 MAXALT Tablets (rizatriptan benzoate) In: Physicians Desk Reference, 53rd ed., , 1999
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39 (mg/) / DMSOdimethyl sulfoxide NF nitrofurantoin NT SN sodium nitrite 2A 2-anthramine CTN 9AA 9-aminoacridine ENNGN-ethyl-N -nitro-nitrosoguanidine 2NF 2-nitrofluorene
40 (mg/) / NT DMSOdimethyl sulfoxide 2A 2-anthramine
41 (mg/) / DMSOdimethyl sulfoxide NF nitrofurantoin NT SN sodium nitrite 2A 2-anthramine CTN 9AA 9-aminoacridine ENNGN-ethyl-N -nitro-nitrosoguanidine 2NF 2-nitrofluorene
42 (mg/) / NT TOX DMSOdimethyl sulfoxide 2A 2-anthramine CTN
43 (mg/) / DMSOdimethyl sulfoxide NF nitrofurantoin NT SN sodium nitrite 2A 2-anthramine TOX 9AA 9-aminoacridine ENNGN-ethyl-N -nitro-nitrosoguanidine 2NF 2-nitrofluorene
44 (mg/) / NT TOX DMSOdimethyl sulfoxide 2A 2-anthramine
45 (mg/) / DMSOdimethyl sulfoxide NF nitrofurantoin NT SN sodium nitrite 2A 2-anthramine TOX 9AA 9-aminoacridine ENNGN-ethyl-N -nitro-nitrosoguanidine 2NF 2-nitrofluorene
46 (mg/) / NT CTN DMSOdimethyl sulfoxide 2A 2-anthramine
47 [ ] (mg/) / TA100 TA1535 TA98 TA1537 # WP2 uvra pkm101 (DMSO) E 19 E 27 9 E 128 (SN) 2.0 NT 267 NT NT NT (9AA) 0.04 NT NT NT 81 NT (2NF) NT NT 1314 NT NT (NF) NT NT NT NT (ENNG) NT NT NT NT 1961 (DMSO) (2A) E NT NT NT 0.01 NT NT NT 0.1 NT NT NT NT 1236 DMSOdimethyl sulfoxide NF nitrofurantoin NT SN sodium nitrite 2A 2-anthramine 9AA 9-aminoacridine ENNGN-ethyl-N -nitro-nitrosoguanidine 2NF 2-nitrofluorene EEBackground lawn1/2 #TA153710
48 [ ] (mg/) (DMSO) (139) (126) (126) (141) (145) E 91 E 91 E (88**) / TA100 TA1535 TA98 TA1537 # WP2 uvra pkm (18) (15) (14) (17) (25) 33 E (23*) (SN) 2.0 NT (256) (29) (25) (33) (28) (36) (39) (10) 96 (102) (9) (123) (10) (122) (12) 97 (99) 9 E (10*) 97 (94) 7 E C C (7***) (82) NT NT NT (9AA) 0.04 NT NT NT (104) (2NF) NT NT (1011) (NF) (1174) (ENNG) NT NT NT NT NT NT NT NT NT NT NT (1615) DMSOdimethyl sulfoxide NF nitrofurantoin NT SN sodium nitrite 9AA 9-aminoacridine ENNGN-ethyl-N -nitro-nitrosoguanidine 2NF 2-nitrofluorene CCBackground lawn0 EEBackground lawn1/2 #TA *E1 **E ***E1C2
49 [ ] (mg/) (DMSO) (154) (162) (159) (148) (145) (2A) E 154 E 97E(118**) (1719) / TA100 TA1535 TA98 TA1537# WP2 uvra pkm (15) (13) (15) (18) (11) (10) (280) (33) (36) (34) (43) (41) (51) 0.01 NT NT (2735) (10) 97 (100) (14) (12) (123) (125) (10) (110) (8) (97) (12) (85) NT NT NT (365) 0.1 NT NT NT NT (1320) DMSOdimethyl sulfoxide NT 2A 2-anthramine EEBackground lawn1/2 #TA **E NT
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60 Buttler, W.H. (1996): A review of the hepatic tumors related to mixed-function oxidase induction in the mouse, Tox. Pathol., 24, Monro, A. (1996): Are lifespan rodent carcinogenicity studies defensible for pharmaceutical agents?, Exp. Toxic. Pathol., 48,
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68 Rubin, LF. And Weisse, L. (1992): Species differences relevant for ocular toxicity studies. In: Manual of oculotoxicity testing of drugs. Ed. Hockwin O, Green K, Rubin LF., IMITREX Tablets (sumatriptan succinate) In: Physicians Desk Reference, 53 rd ed., , 1999 AMERGE Tablets (naratriptan hydrochloride) In: Physician s Desk Reference, 53 rd ed., , ZOMIG Tablets (zolmitriptan) In: Physician s Desk Reference, 53 rd ed., , Takahashi, M. et al. (1992): Nonneoplastic changes in the testis, In: Pathobiology of the aging rat vol. 1, Ed. By Mohr, U., Dungworth, D.L. and Capen, C.C., ILSI Press, Washington D.C. Muraoka, Y. et al (1977): Histological changes of various organs in aged SD-JCL rats, Exp. Anim., 26, 1-12 Kobayashi, K. et al (1994): Historical control data of spontaneous lesions in beagle dogs, J. Toxicol. Pathol., 7,
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72 -20) mg/kg -5) P mg/kg (24%) (27%) (18%) (mg/dl) * ** T3 (nmol/l) T4 (nmol/l) TSH (ng/ml) t 1/2, phase(hours) (ml/h/kg) # 43.6 ### 8.9 # ### ### ### 13.4 # b) ### ### (1/5) (g) (%) * * (g) (%) ** UDPGT c) ## ### d) e) (µg/ml) AUC0-24h f) (µg.h/ml) 1/ /5 4/ Dunnett * (p<0.05) ** (p<0.01), modified T ++ (p<0.01), Student t # (p<0.05) ## (p<0.01) ### (p<0.001) 10 µm pnp consumption/mg protein/min µg/ml 2424
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