Table 3

Binding kinetic constants of antagonists to wild-type and mutant H₁ receptors

	Wild-Type		Lys¹⁹¹ → Ala¹⁹¹		Thr¹⁹⁴ → Ala¹⁹⁴
	k₊₁^3-a	k₋₁^3-b	t_1/2^3-c	k₊₁^3-a	k₋₁^3-b	t_1/2^3-c	k₊₁^3-a	k₋₁^3-b	t_1/2^3-c
[³H]Mepyramine	513 ± 186	0.86 ± 0.08	0.8	923 ± 204	1.10 ± 0.04^3-160	0.6	443 ± 40	0.21 ± 0.02^3-165	4
Levocetirizine	2.3 ± 0.4	0.005 ± 0.002	142	5.9 ± 1.2^3-160	0.052 ± 0.026^3-150	13	7.1 ± 1.8^3-160	0.007 ± 0.002	107
(S)-Cetirizine	1.6 ± 0.7	0.12 ± 0.05	6	4.6 ± 1.4^3-150	0.69 ± 0.29^3-150	1.0	5.0 ± 1.3^3-160	0.030 ± 0.013^3-150	24
(S)-Hydroxyzine	25 ± 2	0.47 ± 0.15	1.5	N.D.	N.D.	N.D.	73 ± 52	0.15 ± 0.10^3-150	5
(R)-Hydroxyzine	13 ± 2	0.022 ± 0.006	31	66 ± 21^3-150	0.042 ± 0.008^3-150	17	66 ± 15^3-160	0.015 ± 0.004	47
(R)-ucb 29992	70 ± 12	0.097 ± 0.04	7	81 ± 9	0.070 ± 0.013	10	131 ± 41	0.088 ± 0.044	8
(S)-ucb 29993	83 ± 32	3.313 ± 2.01	0.2	N.D.	N.D.	N.D.	180 ± 166	0.87 ± 0.52	0.8
Terfenadine	10 ± 5	0.019 ± 0.009	37	30 ± 11^3-150	0.054 ± 0.024^3-150	13	N.D.	N.D.	N.D.
Fexofenadine	1.2 ± 0.3	0.011 ± 0.004	62	2.2 ± 0.6^3-150	0.031 ± 0.006^3-160	22	N.D.	N.D.	N.D.
Loratadine	3.6 ± 0.6	0.13 ± 0.02	5	5.8 ± 0.2^3-150	0.045 ± 0.013^3-150	15	N.D.	N.D.	N.D.

Results are the mean ± S.D. of three experiments. Data were analyzed according to the model proposed by Motulsky and Mahan (1984)as described under Materials and Methods. k ₋₁ for [³H]mepyramine were measured directly in separate experiments and kept constant in the model.P values were obtained from two-tailed, unpaired Studentt tests comparing results from mutant receptors with those of wild-type receptors.

↵3-a , Association kinetic constants are expressed in min⁻¹ × 1 × μmol⁻¹.
↵3-b , Dissociation kinetic constants are expressed in min⁻¹.
↵3-c , Dissociation half-time is expressed in min and was calculated as ln 2/k ₋₁.
↵3-150 , p < 0.05.
↵3-160 , p < 0.01.
↵3-165 , p < 0.001.