PT  - JOURNAL ARTICLE
AU  - S. Z. LANGER
AU  - U. TRENDELENBURG
TI  - DECREASE IN EFFECTIVENESS OF PHENOXYBENZAMINE AFTER CHRONIC DENERVATION AND CHRONIC DECENTRALIZATION OF THE NICTITATING MEMBRANE OF THE PITHED CAT
DP  - 1968 Oct 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 290--299
VI  - 163
IP  - 2
4099  - http://jpet.aspetjournals.org/content/163/2/290.short
4100  - http://jpet.aspetjournals.org/content/163/2/290.full
SO  - J Pharmacol Exp Ther1968 Oct 01; 163
AB  - Chronic denervation and chronic decentralization of the nictitating membrane of the pithed cat reduced the ability of phenoxybenzamine to antagonize responses to injected norepinephrine. However, 2 days after denervation there was no change in the effectiveness of phenoxybenzamine, although the denervation type of supersensitivity is fully developed at that time. Hence, the presynaptic changes responsible for this type of supersensitivity fail to influence the effect of phenoxybenzamine. The decrease in the ability of phenoxybenzamine to antagonize sympathomimetic amines developed in parallel with the development of decentralization supersensitivity. It was observed for both injected norepinephrine and phenylephrine as well as for norepinephrine released by postganglionic stimulation. The observations with phenylephrine indicate that catechol-O-methyl transferase cannot play a role in this phenomenon. The decrease in effectiveness of phenoxybenzamine was related to the postsynaptic changes which are typical for decentralization supersensitivity and which also develop after chronic de- nervation. It is suggested that these postsynaptic changes consist of either an increase in the receptor population or in an improvement in the link between activation of the receptor and contraction of the smooth muscle. The present results cannot distinguish between these two possibilities. © 1968 by the Williams & Wilkins Co.