Arrhythmias and antiarrhythmic drugs: Mechanism of action and structure‐activity relationships I

Morgan, P.H.; Mathison, Ian W.

doi:10.1002/jps.2600650402

Cited by 24 publications

(9 citation statements)

References 85 publications

(39 reference statements)

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“…Recrvstallization of the base from cyclohexane-petroleum ether gave a white solid: mp 98-100 °C; NMR (base, CDC1,) h 1.1 [d, 6, C(Ctf3)9], 2.5 3.1 (m. 3. CHNCH2), 3.9-4.3 (m, 3, OCH2CHOH), 7.4-7.7 (m, 2, naphthyl H6j), 7.8 (s, 1, naphthyl H3), 8.0 8.3 (m, 2, naphthyl Hrx8); mass spectrum (salt, 70 eV) m/e (rel intensitv) 419 (2). 417 (2).…”

Section: Methodsmentioning

confidence: 99%

“…It is thought that the lipophilic aromatic ring penetrates into the bilayer of the cell membrane, thereby altering its physicochemical properties, while the protonated nitrogen interacts with some polar group at the exterior of the membrane, possibly displacing calcium ion. 2 The net result of these interactions is to decrease the conductance of the membrane to depolarizing ions.…”

mentioning

confidence: 99%

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Relationship of nonspecific antiarrhythmic and negative inotropic activity with physicochemical parameters of propranolol analogs

Rauls¹,

Baker²

1979

J. Med. Chem.

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In an attempt to separate the nonspecific antiarrhythmic activity of propranolol from its negative inotropic effects, analogues containing hydrophilic and lipophilic substituents on the nitrogen and on the naphthyl ring were prepared and tested in an isolated tissue preparation. Though it had been predicted that analogues containing a very hydrophilic group on the nitrogen would have the highest antiarrhythmic/negative inotropic effect ratio, it was found that both effects increased identically when the lipophilicity of either the nitrogen or ring substituent was increased.

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Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

Relationship of nonspecific antiarrhythmic and negative inotropic activity with physicochemical parameters of propranolol analogs

Rauls¹,

Baker²

1979

J. Med. Chem.

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“…Besides drugs with class I anti-Discussion arrhythmic activity (for example, lignocaine, procaineamide, and so on), other drugs are known to The results of these studies indicate that mianserin prolong the Q-Tc interval: for example, prenylamine hydrochloride seems to have little effect on the CVS (Bens, 1973) and also drugs that prolong repolarization compared with known TADs. In the volunteer study (for example, amiodarone; Morgan & Mathison, 1976). the only consistent change shown by mianserin was…”

Section: Effect In Hypertensive Patientsmentioning

confidence: 99%

Cardiovascular responses to mianserin hydrochloride: a comparison with tricyclic antidepressant drugs.

Burgess,

Turner,

Wadsworth

1978

Brit J Clinical Pharma

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1. The cardiovascular responses of mianserin hydrochloride and tricyclic antidepressant drugs were investigated using non‐invasive methods of cardiac investigation. A study of the interaction of mianserin and antihypertensive drug therapy is reported. 2. In six normal volunteers, mianserin hydrochloride 20 mg was shown to prolong the corrected Q‐T interval at 150 min (P less than 0.001). It did not affect heart rate, systolic time intervals or the peak normalized derivative of the apexcardiogram. Amitriptyline 50 mg increased the corrected pre‐ejection period interval (PEPI) and the PEP/left ventricular ejection time (LVET) ratio of the systolic time intervals at 150 min (P less than 0.001). Q‐T interval was shortened at 90 minutes. 3. In a double‐blind patient study, clomipramine increased heart rate, P‐R interval, QRS and corrected Q‐T interval in one patient at 2 weeks. Mianserin prolonged corrected Q‐T interval at 1 week but this returned to the pretreatment time by 2 weeks in two patients. 4. In an open study, mianserin 20 mg three times daily did not antagonize the hypotensive action of propranolol or propranolol and hydrallazine in three patients. 5. In a double‐blind study in three patients with desmethylimipramine 25 mg three times daily, mianserin 20 mg three times daily did not antagonize the hypotensive action of either guanethidine or bethanidine.

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“…In order to change the acidic nature of DPH to a basic one, a tertiary nitrogen atom was introduced. Placing a carbonyl group next to the amide nitrogen atom, in a spacer between phenyl groups and easily protonated tertiary nitrogen atom, assured the presence of well-recognised [10][11][12][13][14] , biologically important, functional groups common to the antiarrhythmics. Synthesis of these compounds has been described previously [15,16] .…”

Section: Introductionmentioning

confidence: 99%

Structure-Activity Relationship of Some New Anti-Arrhythmic Phenytoin Derivatives

Ciechanowicz-Rutkowska

Stadnicka

Kieć‐Kononowicz

et al. 2000

Arch. Pharm. Pharm. Med. Chem.

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The pharmacological activity of nine anti‐arrhythmic phenytoin derivatives was assessed in preventing chloroform‐induced arrhythmia. The compounds were tested in vitro on isolated heart of the rat. Four compounds were chosen as representative of the spatial characteristics of the studied group, and X‐ray structure analyses were carried out on them. Because the protonated form is present in physiological milieu, conformational analysis was performed on the protonated form of the four representatives and in addition on the compound showing the highest anti‐arrhythmic activity. It was found that substitution of the imidazolidinone ring of phenytoin at position 3 by a chain containing a tertiary amine nitrogen atom changes the affinity profile from inactivated (phenytoin‐like) to activated (quinidine‐like) cardiac sodium channels. The activity of the studied compounds relies on the presence of protonated tertiary nitrogen atom, at least one phenyl ring, and flexibility of the molecule, which enables the spacer to assume a desired length.

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Arrhythmias and antiarrhythmic drugs: Mechanism of action and structure‐activity relationships I

Cited by 24 publications

References 85 publications

Relationship of nonspecific antiarrhythmic and negative inotropic activity with physicochemical parameters of propranolol analogs

Relationship of nonspecific antiarrhythmic and negative inotropic activity with physicochemical parameters of propranolol analogs

Cardiovascular responses to mianserin hydrochloride: a comparison with tricyclic antidepressant drugs.

Structure-Activity Relationship of Some New Anti-Arrhythmic Phenytoin Derivatives

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