N-830

Related to guanethidine (I) and bretylium (II), the tropine derivative N-(4-phenylbenzyl)-3-benzoyl-a-tropinium bromide (N 361) had a strong ganglion-stimulat-ing effect and produced pressor effect followed by long lasting hypotension when given in almost toxic doses, and hence therapeutically useless.Two related substances, N^α-ethyl - N_β-(4-cyclohexylbenzyl)-3-benzoylnor-α-tropinium bromide (N 830), and N-(4-cyclohexylbenzyl)-3-(p-tolyl)-α-tropinium bromide (N 856) were selective in their action on adrenergic neurons. In anesthetized cats 1-3 mg./kg. of N 830 caused a slight and transient rise in blood pressure not exceeding 25 mm. and lasting 20-5 sec.; 1-1.5 mg./kg. N 856 had no pressor effect, while at 2 mg./kg. the effect was same like that of N 830; however, the action was less significant than that of I and II.Both compounds at a dose of 1 mg./kg. brought the blood pressure from 140-6 mm. to 100 mm. within a few min., while with 2 mg./kg. it came down to 70 mm. and the fall lasted 2 hrs. Both compounds blocked the reflex rise in blood pressure due to carotid occlusion, were active in both anesthetized and unanesthetized animals, and were active in dogs, rats, and cats.The compounds did not antagonize the actions of acetylcholine in the cat or in the isolated rat intestine, did not affect respiration, and at hypotensive-dose levels had no action on the responses of the tibialis anterior muscle to stimulation of the sciatic nerve.Compared with I and II, N 830 and N 856 produced a very transient rise in blood pressure, hypotension lasting much longer, and a rapid onset of action on oral administration. Unlike other quaternary ammonium compounds they are rapidly absorbed from the gastrointestinal tract and are excreted slowly.The compounds are relatively nontoxic, L.D.₅0 in mice being greater than 20 mg./kg., which is larger than that of I and II; and due to smaller hypotensive doses have better therapeutic indexes than I and II.