Summary1. The ,8-adrenoceptor blocking properties of (± )-1-(2-acetyl-4-n-butyramidophenoxy)-2-hydroxy-3-isopropylaminopropane hydrochloride (M&B 17,803A) have been compared with those of practolol and propranolol in the guinea-pig. cat and dog. 2. Following either intravenous or oral administration in the cat or dog, M&B 17,803A and practolol had similar potency in antagonizing isoprenalineinduced tachycardia and both showed cardioselectivity, but both were less potent than propranolol. 3. M&B 17,803A and practolol had approximately one hundredth the intravenous potency of propranolol in increasing the severity of anaphylactic bronchospasm in the conscious sensitized guinea-pig. 4. M&B 17,803A possessed less marked intrinsic sympathomimetic activity than practolol but, like propranolol, it had significant local anaesthetic properties and increased the refractory period of rabbit isolated atria.

1.HCI ( 2 g) treat,ed as above gave 33.AcOH (0.23 g), mmp l l l " , and 33 (0.6 g), mmp 106", by fractional crystallization. The mother liquors were separated chemically to give a nonbasic part which yielded 45 (0.6 g), mmp 85' from EtOAc-petroleum ether.b.-AcC1 (1.57 g, 1 equiv) in CaHjN (10 ml) was added to 33 (4.58 g) in CZHSN (25 ml) at 0". After 18 hr E t 2 0 (100 ml) was added and t'he solution n-as washed with 2 S HC1. The Et20 solut,ion gave a gum containing ester impurity (ir). MeOH (90 ml) and SaOII (lo%, 5.8 ml) were added. After 2.5 hr the LleOH was evaporated in vacuo, Et20 was added, and the Et& solution was washed with 2 iV HC1. The Et?O sollition gave 45, mp 86-87" from EtOAc-petroleum ether (bp 40-60'). Anal. (CnHII-S-[2-Isopropylamino-l-( 2-naphthyl )ethyl] isothiourea .2HC1(12).-Compo~ind 1 (4 g) and thiourea (1.1 g) in EtOH (150 ml) were heated under reflux for 9 hr and tben the EtOH was evaporated to give 12.2-Isopropylamino-l-( 2-naphthy1)ethanethiol ( 13).-Compound 12 (3.8 g), 1 IT NaOH (63 ml), and MeOH (200 ml) were heated ririder reflm for 4 hr and then the XeOH was evaporated. Et,,O extraction gave 13, converted into its HCl by Et,20-HCl: iimr 7 2.15-2.80 (multiplet, ArH , 7 ) , 6.25 (X part of ABX, SCH<, l ) , 7.85-7.97 (multiplet, AB part of ABX, CHzS, 2 ) , 7.20-7.60 (septet, i-Pr CH, l), 8.72 (singlet, T1" and SH, 2 ) , 9.08 and 9.13

The β‐adrenoceptor blocking agent, acebutolol (M & B 17,803), has been compared with propranolol, practolol, lignocaine and quinidine for its ability to revert or prevent various types of experimental arrhythmias. By intravenous infusion, acebutolol had one half the potency of propranolol in reverting an established ouabain‐induced ventricular arrhythmia in the anaesthetized dog. Practolol was ineffective in the conditions used. High oral doses of acebutolol or propranolol significantly increased the arrhythmic dose of ouabain in the conscious rabbit. Similar doses of practolol produced a significant decrease (i.e. potentiation) in the dose of ouabain required to produce arrhythmia. Lignocaine and quinidine showed no or little activity in this test. Propranolol, acebutolol and practolol were all effective in decreasing the frequency of ectopic beats induced by adrenaline and methylchloroform in the anaesthetized cat. Lignocaine and quinidine were only weakly effective. Acebutolol and propranolol were equally effective either intravenously or orally in reducing the incidence of ventricular fibrillation produced by chloroform in mice. It is suggested that the wide spectrum of experimental anti‐arrhythmic activity of acebutolol coupled with its cardioselectivity may make it an interesting compound in the treatment of cardiac arrhythmias in man.

A series of 1-(2-acyl-4-acylaminophenoxy)-3-isopropylaminopropan-2-ols has been synthesized and examined for beta-receptor blocking and antiarrhythmic activity. Several of these compounds are more than 20 times as active in blocking cardiac beta-receptors than vascular beta-receptors when given intravenously to anesthetized cats. The activities have been correlated quantitatively with partition and steric substitution constants. The observed relationships are consistent with a tentative proposal that the vascular receptor is situated in a more lipophilic environment than the cardiac receptor so that there is a differential transport effect between the two types of receptor.

No abstract