Reduction of beta-adrenergic receptors can explain the lack of rebound effect after tertatolol withdrawal.

Tertatolol is a potent beta-blocker with no intrinsic sympathomimetic activity (ISA) or beta 1/beta 2 receptor subtype selectivity. We provide evidence that tertatolol competitively inhibits beta-adrenergic receptors (beta-AR) and induces a marked and persistent reduction of their number. This has been consistently found in vitro and in vivo. The in vitro study showed that the receptor reduction by tertatolol was rapid (about 1 h at 37 degrees C), slowly reversible and independent of ISA. This effect was also observed in vivo. In healthy volunteers, seven days tertatolol treatment lowered the number of beta-AR by 26%. This number gradually rose back to the pretreatment levels, and a significant effect was still present on day 3 after drug withdrawal. The reduction of heart rate by tertatolol was also persistent and was still significant on day 3 to 5 after drug withdrawal. We conclude that the reduction of the receptor numbers may be important in producing a lack of a rebound effect after discontinuation of chronic tertatolol treatment.