PHARMACOLOGY OF THE NEW β-BLOCKERS
1
PHA RM ACOLOGY OF THE NEW . .. Effe ct s Of Atenolol And Pra ctolol on Ex erci se Tachycardia A consistently linear dose-response was found for cumulative doses of atenotot (O.12mg/ kg) and praetolol (O.4mg/kg ) given as a continuous IV infusion between 7 and 12 mins of bicycle exercise.This may bea useful technique for assessing the relative potency of antago nists. The study was controlled against a saline infusion and conducted in 4 healthy volunteers. Effects were measuredagainstexercise tachyca rdia produced by bicycle exercise. Mean heart rate at 7min for practolo\ ( 133 bprnj and atenclol (J 32 bpm) reduced to 115 and 104 bpm respectively (p < 0.1). There was no change with saline.The llatter log dose-responsecurve for practolol may be a resu lt o f its agonist activity. Myers. MG . Georte. C.f.: In lCTNUoMl Joll rtWofOi nical Plwmae:olol:r 14, 266(0« 1916) . . . And Of Propranolol. Met op rolol and Praetolol In another Sludy in 6 normal volunteers, single oral doses of SOmg proprano\ol, 2S0mg practolol and 1000g metoprojcl were found to be equipotent in the ir ability to inhibit cxercise-induced tachycardia. Man resting heart rate was 74 .3 and after exercise , 153.8. All compounds reduced the rate by about 30 %. 1be blocking eff ects wert manifest at plasma JevelsofS0-60ng/ml propranolol. 1050· 11OOng /ml praetotol and 140-1 SOng/ rot met oprolol. So. for praetolol it required about 20 times the blood levels of pro p ra nolo l and 7 times those of metoprolol to produce the same effect after a single oral dose. In contrast to practnl ol, proprano lol and metoprolol (both of which are devoid of partial agonist aetivity)causcd sign ifkant depression in the rest ing heart rat e. Th e au thors oondude ' .. . rM data shOWing that metoprokH a almost as potent as proprarrololand mor(' porent than pracioiol in inhibiting exercise -induced tachycardia in ht'tlJ/hy subjects have ther- a{'t'U/ic implicQ/ions me/oproJoi lik.eprac/olol has beenfound /0 htWe leu in patien ts with a irll'Q) 's obstrucuon the role of an ouemouve cardioseiecttve j)-adrenor «eptor amagonis/ such as me/oprolof in clinical therapeutics merits de/ailed investigation.' Wi lliam" f .M. d ai" Oinica1-..d I'l».nnac:oIoc and Pb)'Siolo&y 3, 473 (Sop 1976) INPHARMA 1 5th Jal'lUluy. 1971 p15
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Transcript of PHARMACOLOGY OF THE NEW β-BLOCKERS
PHARM ACOLOGY OF THE NEW ~ .BLOCKERS
. .. Effects Of Atenolol And Practolol on Exercise Tachyca rdiaA consistently linear dose-response was found for cumulative doses of atenotot (O.12mg/kg) and praetolol(O.4mg/kg)given as acontinuous IV infusion between 7 and 12mins of bicycle exercise.This may bea useful technique for assessing the relativepotency of ~.adrenoreceptor antago nists.The study was controlled against a saline infusion and conducted in 4 healthy volunteers. Effects were measuredagainstexercisetachycardia produced by bicycle exercise. Mean heart rate at 7min for practolo\ (133 bprnj and atenclol (J 32 bpm) reduced to 115and 104 bpm respectively (p < 0.1). There was no change with saline.The llatter log dose-responsecurve for practolol may be aresu lt of its agonist activity.
Myers. MG.~ Georte.C.f.: InlCTNUoMl JollrtWofOinical Plwmae:olol:r 14 , 266(0« 1916)
. . . And Of Propranolol. Metoprolol and PraetololIn another Sludy in 6 normal volunteers, single oral doses of SOmg proprano\ol, 2S0m g practolol and 1000g metoprojcl werefound to be equipotent in the ir ability to inhibit cxercise-induced tachycardia. Man resting heart rate was 74 .3 and after exercise ,153 .8. All compounds reduced the rate by about 30% . 1be blocking effects wert manifest at plasma JevelsofS0-60ng/mlpropranolol. 1050· 11OOng/ml praetotol and 140-1 SOng/ rot met oprolol. So. for praeto lol it required about 20 times the bloodlevels of propranolo l and 7 times those of metoprolol to produce the same effect after a single oral dose . In contrast to practnl ol,proprano lol and metoprolol (both of which are devoid of partial agonist aetivity) causcd sign ifkant depress ion in the rest ing heartrat e.
The au thors oondude '.. . rM data shOWing that metoprokHa almost as potent as proprarrololand mor(' porent than
pracioiol in inhibiting exercise -induced tachycardia in ht'tlJ/hy subjects have ther-a{'t'U/ic implicQ/ions me/oproJoi
lik.eprac/olol has beenfound /0 htWeleu bro"cho~pa~tic effec/~ in patien ts with a irll'Q) 's obstrucuon the role ofan
ouemouve cardioseiecttve j)-adrenor«eptor amagonis/ such as me/oprolof in clinical therapeutics merits de/ailedinvestigation. '
Wi lliam" f .M. d ai" Oinica1-..d &po:rime~ I'l».nnac:oIoc and Pb)'Siolo&y 3, 473 (Sop 1976)
INPHARMA 15th Jal'lUluy. 1971 p15
