Summary
Ten patients (44 y), 6 with the Wolff-Parkinson-White syndrome, and none with hypertensive disease, underwent electrophysiological studies before and after intravenous infusion of a single dose of 1 mg rilmenidine administered over 15 min.
The regimen produced a mean plasma rilmenidine concentration of 3.16 ng·ml−1 at the end of the infusion. There was no significant change in sinus cycle length, PR interval, QRS, QT duration or in PA, AH and HV intervals. Estimated sinoatrial conduction time and corrected sinus node recovery time did not significantly change. In one patient, however, an abnormal pause was noted after termination of rapid atrial pacing. The right atrial effective refractory period decreased from 209 to 194 ms. There was no significant change in the anterograde and retrograde block cycle length or in the refractoriness of the nodal, ventricular and accessory pathways. The cycle length of induced reciprocating tachycardia decreased slightly from 374 to 351 ms. No patient exhibited an abnormal response to the carotid sinus massage.
The findings indicate that intravenous administration of 1 mg rilmenidine exerts modest effects on the electrophysiological parameters of the human heart.
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References
Bricca G, Dontenwill M, Molines A, Feldman J, Tibirica E, Belcourt A, Bousquet P (1989) Rilmenidine selectivity for imidazoline receptors in human brain. Eur J Pharmacol 163: 373–377
Lachaud V, Coupry I, Podevin RA, Dausse JP, KoenigE, PariniA (1988) Interaction of clonidine and rilmenidine with imidazoline-preferring receptors. J Hypert [Suppl 4]: S511–S513
Van Zwieten PA (1988) Pharmacology of the alpha2-adenoceptor agonist rilmenidine. Am J Cardiol 61: 6D-14D
Verbeuren TJ, Dinh Xuan AT, Koenig-Berard E, Vitou P (1990) Rilmenidine. Cardiovasc Drug Rev 8: 56–70
Bousquet P, Feldman J, Tibirica E, Bricca G, Molines A, Dontenwill M, Belcourt A (1989) New concepts on the central regulation of blood pressure. Am J Med 87 (3C): 10S-13S
Safar ME (1989) Rilmenidine: a novel antihypertensive agent. Am J Med 87 (3C): 24S-29S
Koenig-Berard E, Tierney C, Beau B, Delbarre G, Lhoste F, Labrid C (1988) Cardiovascular and central nervous system effects of rilmenidine (S3341) in rats. Am J Cardiol 61: 22D-31D
Zannad F, Aliot E, Florentin J, Saulnier J-P, Gilgenkrantz J-M (1988) Hemodynamic and electrophysiologic effects of a new alpha2-adrenoceptor agonist, rilmenidine, for systemic hypertension. Am J Cardiol 61: 67D-71D
Narula OS, Shantha N (1980) Atrioventricular block: clinical concepts and his bundle electrocardiography. In: Mandel WJ (ed) Cardiac arrhythmias. Their mechanismes, diagnosis, and management. Lippincott, Philadelphia, pp 437–453
Strauss HC, Scheinman MM, Labarre A, Browning DJ, Benditt DG, Wallace AG (1978) Programmed atrial stimulation and rapid atrial pacing in patients with sinus pauses and sinoatrial exit block. In: Bonke FIM (ed) The sinus node. Structure, function and clinical relevance. Nijhoff, The Hague, pp 56–64
Narula OS, Shantha N, Narula LK, Alboni P (1979) Clinical and electrophysiological evaluation of sinus node function. In: Narula OS (ed) Cardiac arrhythmias. Electrophysiology, diagnosis and management. Williams and Wilkins, Baltimore, pp 176–206
Narula OS (1979) Electrophysiology of normal impulse propagation. In: Narula OS (ed) Cardiac arrhytmias. Electrophysiology, diagnosis and management. Williams and Wilkins, Baltimore, pp 57–65
Genissel P, Bromet N, Fourtillan J-B, Mignot A, Albin H (1988) Pharmacokinetics of rilmenidine in healthy subjects. Am J Cardiol 61: 47D-53D
Singlas E, Ehrhardt J-D, Zech P, Pozet N, Genissel P (1988) Pharmacokinetics of rilmenidine. Am J Cardiol 61: 54D-59D
Ehrhardt JD (1985) Gas chromatography negative ion mass spectrometric assay of 2-dicyclopropylmethylamino-2-oxazoline (S3341), a new antihypertensive drug. Biomed Mass Spectrom 12 (10): 593–595
Ung HL, Girault J, Lefebvre MA, Mignot A, Fourtillan JB (1987) Quantitative analysis of S3341 in human plasma and urine by combined gas chromatography-negative ion chemical ionization mass spectrometry: 15 month inter-day precision and accuracy validation. Biomed Mass Spectrom 14: 289–293
Weerasuriya K, Shaw E, Turner P (1984) Preliminary clinical pharmacological studies of S3341, a new hypotensive agent, and comparison with clonidine in normal males. Eur J Clin Pharmacol 27: 281–286
Montastruc J-L, Macquin-Mavier I, Tran M-A, Damase-Michel C, Koenig-Berard E, Valet P (1989) Recent advances in the pharmacology of rilmenidine. Am J Med 87 (3C): 14S-17S
Atlas D, Burstein Y (1984) Isolation and partial purification of a clonidine-displacing endogenous brains susbtance. Eur J Biochem 144: 287–293
Bousquet P, Feldman J, Schwartz J (1984) Central cardiovascular effects of alpha-adrenergic drugs: differences between catecholamines and imidazolines. J Pharmacol Exp Ther 230–236
Ernsberger PR, Meeley MP, Reis DJ (1986) An endogenous clonidine-like substance binds preferentially to imidazole binding sites in the ventrolateral medulla labelled by 3H-para-aminoclonidine. J Hypertens 4: S109-S111
Van Zwieten PA, Thoolen MJMC, Jonkman FAM, Wilffert B, De Jonge A, Timmermans PBMWM (1986) Central and peripheral effects of S3341 (N-dicyclopropylmethyl)-amino-2-oxazoline in animal models. Arch Int Pharmacodyn Ther 279: 130–149
N'Guyen van cao A, Levy B, Slama R (1988) Noninvasive study of cardiac structure and function after rilmenidine for essential hypertension. Am J Cardiol 61: 72D-75D
Tonet JL, Frank R, Fontaine G, Lajeuncomme MR, Vedel J, Petitot JC, Coutte R, Grosgogeat Y (1983) Evaluation de la réponse au test à l'ajmaline dans le diagnostic des blocs atrioventriculaires paroxystiques. Arch Mal Coeur 10: 1154–1162
De Jonge A, Timmermans PBMWM, Van Zwieten PA (1981) Participation of cardiac presynaptic alpha2-adrenoceptors in the bradycardiac effects of clonidine and analogues. Naunyn-Schmiedebergs Arch Pharmacol 317: 8–12
Kobinger W (1989) Specific bradycardic agents. In: Vaughan Williams EM (ed), Antiarrhythmic drugs. Springer, Berlin Heidelberg New York, pp 435–452
Primm RK, Urthaler F, James TN (1980) Selective effects of clonidine on the canine sinus node. Pharmacol Exp Ther 214: 223–228
Scheinman MM, Strauss HC, Evans GT, Ryan C, Massie B, Wallace A (1978) Adverse effects of sympatholytic agents in patients with hypertension and sinus node dysfunction. Am J Med 64: 1013–1020
Thormann J, Neuss H, Schlepper M, Mitrovic V (1981) Effects of clonidine on sinus node function in man. Chest 80: 201–206
Victor J, Foussard C, Bouvier A, Tadei A (1985) Influence de la clonidine intraveineuse sur les noeuds sinusal et auriculo-ventriculaire normaux et pathologiques et sur la sensibilité sinocarotidienne. Arch Mal Coeur 4: 637–643
Kibler LE, Gazes PC (1977) Effect of clonidine on atrioventricular conduction. JAMA 238: 1930–1932
Williams PL, Krafcik JM, Potter BB, Hooper JH, Hearne MJ (1977) Cardiac toxicity of clonidine. Chest 72: 784–785
Clementy J, Castagne D, Wicker P, Dallocchio M, Bricaud H (1983) Etude des propriétés électrophysiologiques de la clonidine administrée par voie veineuse. Arch Mal Coeur 76: 151–156
Toussaint C, Cave D, Saoudi N, Moore N, Letac B (1984) Electrophysiological effects of intravenous clonidine on sinus node function and conduction in man. J Cardiovasc Pharmacol 6: 56–60
Vaughan Williams EM (1988) Adrenergic arrhythmogenicity. Eur Heart J 9 (B): 33–36
Dukes ID, Vaughan Williams EM (1984) Effects of selective alpha1-, alpha2-, beta1- and beta2- adrenoceptor stimulation on potentials and contractions in the rabbit heart. J Physiol 355: 523–546
McGrath JC (1989) Alpha-adrenoceptors in arrhythmogenesis. In: Vaughan Williams EM (ed) Antiarrhythmic drugs. Springer, Berlin Heidelberg New York, pp 481–518
Jarrott B, Lewis SJ, Doyle AE, Louis WJ (1988) Effects of continuous infusions (10 days) and cessation of infusions of clonidine and rilmenidine (S3341) on cardiovascular and behavioral parameters of spontaneously hypertensive rats. Am J Cardiol 61: 39D-44D
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Tonet, J., Guillet, C., Jondeau, G. et al. Electrophysiological effects of intravenous rilmenidine in man. Eur J Clin Pharmacol 41, 537–540 (1991). https://doi.org/10.1007/BF00314981
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DOI: https://doi.org/10.1007/BF00314981