DIMETHYL 4,4'-METHYLENEBIS(PHENYLCARBAMATE) 1975 References BLACKWELL, J. • GARDNER, K. H. (1979). Polymer, 20, 13-17. BONART, R., MORBITZER, L. & MULLER, E. H. (1974). J. Macromol. Sci. Phys. 9, 447-461. CHAUDHURI, I . & HARGREAVES, A. (1956). Acta Cryst. 9, 793-800. CORFIELD, P. W. R., DOEDENS, R. J. & IBERS, J. A. (1967). Inorg. Chem. 6, 197-204. FRENZ, B. A. (1978). The Enraf-Nonius CAD-4 SDP - a Real-Time System for Concurrent X-ray Data Collection and Crystal Structure Determination. Computing in Crystallography, edited by H. SCHENK, R. OLTHOF- HAZEKAMP, H. VAN KONINGSVELD & G. C. BASSI, pp. 64-71. Delft Univ. Press. International Tables for X-ray Crystallography (1974). Vol. IV, Table 2.2B. Birmingham: Kynoch Press. SWARDSTROM, J. W., DUVALL, L. A. & MILLER, D. P. (1972). Acta Cryst. B28, 2510-2514. WHITTAKER, E. J. W. (1953). Acta Cryst. 6, 714-720. Acta Cryst. (1980). B36, 1975-1977 Cyclizine Hydrochloride* BY V. BERTOLASI Istituto Chimico, Universit~t di Ferrara, Italy P. A. BOREA Istituto di Farmacologia, Universit~t di Ferrara, Italy AND G. GILLI AND M. SACERDOTI Centro di Strutturistica Diffrattometrica, Universitgt di Ferrara, Italy (Received 19 December 1979; accepted 21 March 1980) Abstract. C1sH23N+.CI -, Pnma, a = 11.833 (3), b = 13.631 (3), c = 10.023 (3) A, Z = 4, D c = 1.24 Mg m -3,/l(Mo Ks) = 0-191 mm -~. The molecule lies on a crystallographic plane of symmetry and the crystal structure is held together by van der Waals packing of ion pairs linked by hydrogen bonds. The distance of 6.03 A between the protonated N atom and the centroid of the phenyl ring is close to those observed in other antihistamines belonging to different chemical classes, but does not correspond to that observed in histamine itself. The final R was 0.047. Introduction. Antihistamines, or, more precisely, H 1 histamine receptor antagonists, are a class of drugs able to antagonize competitively the effects of histamine at the HI receptor site. In many cases agonists and their competitive antagonists show remarkable chemical similarities, but this similarity has been questioned (Ariens, 1977) for antihistaminic agents, which do not appear to mimic histamine and its agonists. Never- theless, chemical and stereochemical similarities can be * Crystallographic and Conformational Studies on Histamine H 1 Receptor Antagonists. II. 0567-7408/80/081975-03501.00 found among antihistamines themselves, in spite of the fact that they belong to at least five different chemical classes. In general, it is assumed (Witiak, 1970) that the pharmacodynamic part of antihistamines can be reduced to Ar2X-C-C-N ÷ (where X = N, C-O or CH). Reports in the literature suggest (Witiak, Muhi- Eldeen, Mahishi, Sethi & Gerald, 1971) that the presence of two aromatic rings is useful for the enhancement of antihistaminic activity but that stron- gest antagonism occurs only when at least one ring is able to assume a fixed distance from the amino N atom. From crystal structure determinations of histadyl hydrochloride (Clark & Palenik, 1972), (+)-brom- pheniramine maleate (James & Williams, 1971), (+)-chlorpheniramine maleate (James & Williams, 1974a) and triprolidine hydrochloride (James & Wil- liams, 1974b), the distance between the amino N and the centroid of one of the unsaturated rings is found to lie in the range 6-6.40 ,/k (James & Williams, 1974b). In a recent paper (Bertolasi, Borea, Gilli & Sacerdoti, 1980) we have reported the crystal structure of carbinoxamine maleate, which belongs to the class of the aminoethyl ether derivatives, and have shown that a similar distance of 6.30 A is found in this molecule. © 1980 International Union of Crystallography