[³H]RS79948-197 binding to human, rat, guinea pig and pig α(2A)-, α(2B)- and α(2C)-adrenoceptors. Comparison with MK912, RX821002, rauwolscine and yohimbine

The K(d) values of the recently introduced radioligand [³H]RS79948-197 ((8aR,12aS,13aS)-5,8,8a,9,10,11,12,12a,13,13a-decahydro-3-methoxy-12- (ethylsulphonyl)-6H-isoquino[2,1-g][1,6]naphthyridine) were determined for the recombinant human and rat α(2A)-, α(2B)- and α(2C)- as well as guinea pig α(2B)- and α(2C)-adrenoceptors expressed in COS (CV-1 Origin, SV40) cells. In addition, the K(d) values were also determined for [³H]RS79948- 197 for the guinea pig spleen α(2A)-adrenoceptor and for pig α(2A)-, α(2B)- and α(2C)-adrenoceptors in membranes obtained from kidney and striatum. Available radioligands for α₂-adrenoceptors, besides [³H]RS79948-197 are the tritiated forms of MK912 ((2S,12bS)1',3'- dimethylspiro(1,3,4,5',6,6',7,12b-octahydro-2H-benzo[b]furo[2,3- a]quinazoline)-2,4'-pyrimidin-2'-one), RX821002 (2-methoxy-idazoxan), rauwolscine and yohimbine. In the present article the binding constants of all these substances for the α(2A)-, α(2B)- and α(2C)-adrenoceptor subtypes in human, pig, rat and guinea pig are reviewed. In all species tested MK912 was α(2C)-selective, RX821002 showed a minor α(2A)- selectivity, whereas [³H]RS79948-197 was non-selective among the α₂- adrenoceptor subtypes, showing high affinity for all three subtypes. Rauwolscine and yohimbine showed relatively low affinities for most of the α₂-adrenoceptor subtypes investigated, the exception being rauwolscine having high affinity for the human and porcine α(2C)-adrenoceptors.