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Fig. 1. Relationship befween ECsos for stimulation of lipolysis and inhibition of colon motf/ity by F-adrenocaptor agonists. Compounds were tested on rat iso!afed colon (see Ref. 6) and on rat white adipoqtes (see Ref. 70): r = 0.97.
ethanolaminotetralines appeared to have much greater selectivity for atypical p-receptors than do lipolytically selective @-adreno- ceptor agonists (see Ref. 2).
The pharmacological character- ization of the recently cloned human ‘&-adrenoceptor’a in trans- fected cultured cells was based on stimulation of CAMP production by several adrenoceptor agonists that was inhibited by CGP20712A
LUCIANO MANARA
AND ALBERT0 BIANCHETTl
Resenrch Center SANOFI-MIDY S.p.A., Vin G.B. Piranesi 38-20137 Milan, Italy.
References 1 Kaumann, A. J. (1989) Trends Pharntncol.
:ci. 10, 316-320 2 Zaagsma, J. and Nahorski, S. R. (1990)
Trends Pharmacol. Sci. 11, 3-7 3 Lands, A. M., Arnold, A., McAuliff,
TiPS - june 1990 [Vol. 221
J. I’., Luduena, F. P. and Brown, T. G. (1967) Nnture 214, 597-598
4 Emorine, L. J. et nl. (1989) Scierzce 245, lllM121
5 Croci, T. et al. (1988) Pharmacol. RP;. CownWZ. 20, i47-151
6 Nlz~ra, L., Bianchrtti, A., Croci, T. and Giudice, A. (1989) in Keurochenkal Dhnrtnacology: A Tribute to B. B. Brodie (Costa, E., ed.), pp. 131-147, Raven Press
? Bianchetti, A. and Manara, L. Br. 1. Pham2ncol. (in press)
8 Arch, J. R. S. ef 01. (1984) Nature 309, 163-165
9 Croci, T., Bianchetti, A., Poggesi, E., Boigegrain, R. and Manara, L. (1987) Dig. Dis. Sci. 32, 907
10 Rodbell, M. (1964) j. Biol. Chem. 239, 753-755
11 Croci, T., Bianchetti, A. and Manara, L. (1988) Pharnwcol. Res. Comnrun. 20 (Suppl. II), 118
12 Giudice, A., Croci, T., Bianchetti, A. and Manara, L. (1989) Z;c Sci. 44, ;:I?-1417
CGP20712A: (f)-l-[2-(3-carbamoyl-4- hydroxyphenoxy)-ethylamino]-3-[4-(l- methyl-4-trifluormethyl-2-imidazolyl)- phenoxyj-2-propanol 1Cl118551: erythro-(+)-l-(7-methylindan- 4-yloxy)-3-isopropylaminobutan-2-oi SR58375A: RR-N-(7-hydroxy-1,2,3,4- tetrahydronaphth-2-yl)-2-hydroxy-2- phenylethanamine; as-isomer, SR58374; ss-isomer, SR58373A SR58572A: RR-N-(7-hydroxy-1,2,3,4- tetrahydronaphth-2-yI)-2-hydroxy-2-(3- chlorophenyl)ethanamine; as-isomer, SR58589; ss-isomer, SR58575A SR58612A: aa-N-(7-carbethoxymethoxyl- 1,2,3,4-tetrahydronaphth-2-yl)-2-hydroxy- 2-(3-chlorophenyl)ethanamine; as-isomer, SR58611A; ss-isomer, SR58613A
and ICI118551 in the micromolar range, but not by alprenolol and Only winning battles, but hoping to win the war
c- - __ _ _ _ _ _ _ -
propranolol; this indicates sub- stantial differences from both the
Jbiectives of radical antivivisectionists? -,----- .
adipocyte atypical fi-adrenocep- torZ and that accounting for the action of phenylethanolamino- tetralines on the rat colon. In this system, however, specific antag- onists were only tested against the least selective P-agonist, isopren- aline.
Efforts to develop the phenyl- ethanolaminotetralines are aimed at therapeutic applications; in- deed in animal models, unlike available P-adrenoceptor agonists, our new compaunds are promis- ing for treating intestinal hyper- motility disorders without cardio- vascular or other side-effects of potential clinical relevance11,12. In addition we hope that these potent and selective agents, whose mechanism of action is discussed in detaii elsewhere7, wi!l serve as a valuable research tool for those investigating p- adrenoceptor multiplicity.
In his recent article (Tips, March 199O)l Gerhard Zbinden writes: ‘Despite recent changes in legislation in several countries and general reduction in the use of animals in biomedical research, the impatience of antivivisectionists to see reduc- tions in animal experimentation shows no signs of abating’.
I believe a more accurate begin- ning for the statement vtouid have been ‘Because of’ rather than ‘Despite’. The stated objective of the radical antivivisectionists is complete elimination of all vivi- section, i.e. of all use of animals in research and of anything else that interferes with the ‘natural life’ of an animal. It is naive to believe that stricter regulations or mere reductions in the number of ani- mals used in research will satisfy the antivivisectionists and reduce their activities. From their view- point, these are only battles with-
in the war. Winning such battles should be expected to increase, not decrease, the desire of the antivivisectionists for complete victory. A way to help assure their victory is for us to remain blind to the history, literature aiid goals of the movement, and thus be con- tinually surprised by the failure of appeasement.
Tiie development of in-vitro methods and testing procedures is a worthy endeavor, for the sake of both aniinals and science. But it should not be undertaken in the vain hope of reducing pressure from antivivisectionists.
DAVID SINCLAXR
Research Laboratories, AI/co Ltd, Helsinki, SF- 00101 Finland.
Reference 1 Zbinden, G. (1990) Trends Pharmacol. Sci.
11,104-107
