RESUMEN
A series of aminoisopropanoloxy derivatives of xanthone has been synthesized and their pharmacological properties regarding the cardiovascular system has been evaluated. Radioligand binding and functional studies in isolated organs revealed that title compounds present high affinity and antagonistic potency for α1-(compound 2 and 8), ß-(compounds 1, 3, 4, 7), α1/ß-(compounds 5 and 6) adrenoceptors. Furthermore, compound 7, the structural analogue of verapamil, possesses calcium entry blocking activity. The title compounds showed hypotensive and antiarrhythmic properties due to their adrenoceptor blocking effect. Moreover, they did not affect QRS and QT intervals, and they did not have proarrhythmic potential at tested doses. In addition they exerted anti-aggregation effect. The results of this study suggest that new compounds with multidirectional activity in cardiovascular system might be found in the group of xanthone derivatives.
Asunto(s)
Antagonistas Adrenérgicos/síntesis química , Diseño de Fármacos , Xantonas/química , Antagonistas Adrenérgicos/metabolismo , Antagonistas Adrenérgicos/farmacología , Animales , Presión Sanguínea/efectos de los fármacos , Bloqueadores de los Canales de Calcio/síntesis química , Bloqueadores de los Canales de Calcio/metabolismo , Bloqueadores de los Canales de Calcio/farmacología , Canales de Calcio/química , Canales de Calcio/metabolismo , Frecuencia Cardíaca/efectos de los fármacos , Concentración 50 Inhibidora , Masculino , Agregación Plaquetaria/efectos de los fármacos , Ensayo de Unión Radioligante , Ratas , Ratas Wistar , Receptores Adrenérgicos alfa/química , Receptores Adrenérgicos alfa/metabolismo , Receptores Adrenérgicos beta/química , Receptores Adrenérgicos beta/metabolismo , Relación Estructura-Actividad , Verapamilo/química , Xantonas/metabolismo , Xantonas/farmacologíaRESUMEN
A series of different 1,4-substituted piperazine derivatives (1-11) was synthesized. It comprised 1-(substituted-phenoxyalkyl)-4-(2-methoxyphenyl)piperazine derivatives (1-5); 1,4-bis(substituted-phenoxyethyl)piperazine derivatives (6-8) and 1-(substituted-phenoxy)-3-(substituted-phenoxyalkylpiperazin-1-yl)propan-2-ol derivatives (9-11). All compounds were evaluated for affinity toward alpha 1- and alpha 2-receptors by radioligand binding assays on rat cerebral cortex using [3H]prazosin and [3H]clonidine as specific radioligand, respectively. Furthermore alpha 1-antagonistic properties were checked for most promising compounds (1-5 and 10) by means of inhibition of phenylephrine induced contraction in isolated rat aorta. Antagonistic potency stayed in agreement with radioligand binding results. The most active compounds (1-5) displaced [3H]prazosin from cortical binding sites in low nanomolar range (Ki = 2.1-13.1 nM). Compound 10 showed slightly lower affinity for alpha 1-adrenoceptor (Ki = 781 nM). Compounds 2-5 displayed the strongest antagonistic activity with pA2 values ranging from 8.441 to 8.807. Compound 1 gave a pA2 value of 7.868, while compound 10 showed the weakest antagonistic potency, giving a pA2 value of 6.374. 1-[3-(2-Chloro-6-methylphenoxy)propyl]-4-(2-methoxyphenyl)piperazine hydrochloride (5) showed the best alpha 1- affinity properties with a Ki(alpha 1) value of 2.1 nM and it was 61.05 fold more selective toward alpha 1 than alpha 2-receptors. The best properties showed 1-[3-(2,6-dimethylphenoxy)propyl]-4-(2-methoxyphenyl)piperazine hydrochloride (4) with a Ki(alpha 1) value of 2.4 nM, a 142.13 fold better selectivity to alpha 1 - over alpha 2-adrenoceptors and the best antagonistic potency (pA2 = 8.807). It is worth to emphasized that all most promising compounds possessed an 1-(o-methoxyphenyl)piperazine moiety which probably plays an important role in the affinity to alpha-adrenoceptors.
Asunto(s)
Antagonistas de Receptores Adrenérgicos alfa 1/farmacología , Piperazinas/farmacología , Receptores Adrenérgicos alfa/metabolismo , Antagonistas Adrenérgicos alfa/metabolismo , Animales , Aorta Torácica/efectos de los fármacos , Aorta Torácica/metabolismo , Bioensayo , Corteza Cerebral/efectos de los fármacos , Corteza Cerebral/metabolismo , Relación Dosis-Respuesta a Droga , Técnicas In Vitro , Indicadores y Reactivos , Masculino , Piperazinas/metabolismo , Ensayo de Unión Radioligante , Ratas , Ratas Wistar , Receptores Adrenérgicos alfa 1/metabolismo , Receptores Adrenérgicos alfa 2/metabolismo , Relación Estructura-ActividadRESUMEN
A series of aroxyethylamines (1-10) have been previously evaluated for antihypertensive and adrenolytic properties. Of the derivatives tested, four (compounds 4, 7, 8 and 10) displayed significant antihypertensive activity and binding affinities for alpha- and beta-adrenergic receptors. As a continuation of our study, we present here the in vivo and in vitro antiarrhythmic activity of compounds 1-10, as well as their electrocardiographic properties. Only compounds 4, 7, 8 and 10 demonstrated strong antiarrhythmic activity in adrenaline induced arrhythmia after intravenous and oral administration. In addition, compounds 4 and 7 significantly decreased heart rhythm disturbances in arrhythmia induced by coronary artery occlusion and reperfusion. The pharmacological results and receptor binding studies suggest that the antiarrhythmic activity of the compounds tested may be related to their adrenolytic properties. Moreover, the presence of a methoxyphenylpiperazine moiety seems to be required for their pharmacological activity.
Asunto(s)
Antagonistas Adrenérgicos/farmacología , Antiarrítmicos/farmacología , Etilaminas/farmacología , Animales , Arritmias Cardíacas/inducido químicamente , Arritmias Cardíacas/tratamiento farmacológico , Enfermedad Coronaria/tratamiento farmacológico , Enfermedad Coronaria/fisiopatología , Electrocardiografía/efectos de los fármacos , Epinefrina , Técnicas In Vitro , Inyecciones Intravenosas , Daño por Reperfusión Miocárdica/tratamiento farmacológico , Ratas , Relación Estructura-ActividadRESUMEN
A series of new 4-arylpiperazine derivatives of isothiazolopyridine of Mannich base type and their non-4-arylpiperazine analogues (3 and 4) were synthesized and assayed as potential analgesic agents. Pharmacological assay demonstrated that all the compounds prepared, without exception, displayed significant activity in the mouse writhing assay. The analgesic action, expressed as ED50, was found to be 2-10 times more potent than that of acetylsalicylic acid and 1.5-10 times weaker than that of morphine, these being used as standards. The toxicities (LD50) of the investigated derivatives varied and ranged from 250 to 2000 mg/kg. Additionally, the computational investigations were performed in order to find correlation between molecular structure and biological effects (toxicity, analgesic action) of discussed compounds. Useful model was found for toxicity assessment.
Asunto(s)
Analgésicos/síntesis química , Bases de Mannich/síntesis química , Piperazinas/síntesis química , Piridinas/síntesis química , Tiazoles/síntesis química , Analgésicos/farmacología , Analgésicos/toxicidad , Animales , Conducta Animal/efectos de los fármacos , Benzoquinonas , Diseño de Fármacos , Evaluación Preclínica de Medicamentos , Calor , Dosificación Letal Mediana , Masculino , Bases de Mannich/farmacología , Bases de Mannich/toxicidad , Ratones , Modelos Químicos , Estructura Molecular , Umbral del Dolor/efectos de los fármacos , Piperazinas/farmacología , Piperazinas/toxicidad , Piridinas/farmacología , Piridinas/toxicidad , Relación Estructura-Actividad , Tiazoles/farmacología , Tiazoles/toxicidadRESUMEN
We prepared a series of new N-[2-(4-substitutedpiperazin-1-yl)ethyl]-1-(n-butyl or phenyl)-2,5-dimethyl-3,4-pyrroledicarboximides 3 and the related products 4 and 5, nine representatives of which were evaluated as potential analgesic agents in an animal model (mice). The new pyrroledicarboximides were not toxic (LD50 > or = 1466 mg/kg) and eight of them displayed analgesic activity approximately 1.5-5 times superior to that of ASA in the writhing test. However, the compounds were found to be unstable in methanol solution and in dilute bases (methanol/NaOMe). The S-A relationship is discussed.
Asunto(s)
Analgesia , Analgésicos/síntesis química , Pirroles/síntesis química , Analgésicos/química , Analgésicos/toxicidad , Animales , Relación Dosis-Respuesta a Droga , Estabilidad de Medicamentos , Dosificación Letal Mediana , Masculino , Ratones , Actividad Motora/efectos de los fármacos , Pirroles/química , Pirroles/toxicidad , Relación Estructura-ActividadRESUMEN
2-Methoxy- and 2-ethoxy-6-methyl-3,4-pyridinedicarboximides (XI, XII) reacted with N-methylhydrazine giving 2- and 3-methyl derivatives of the appropriate 1,4-dioxo-1,2,3,4-tetrahydropyrido[3,4-d]pyridazines (XV, XIII and XVI, XIV). In both cases 3-methyl isomer (XIII, XIV) was formed in higher yield than 2-methyl derivative (XV, XVI). Reaction of the imide XII with N-phenylhydrazine gave the salts of the suitable N-phenyldihydropyrido[3,4d]pyridazines with NH2-NHC6H5 (XXI and XXII) which transformed into N-phenylaminoimide (XXIII) during the boiling in 80% CH3COOH. Imide XXIII isomerized to the appropriate 2-phenyl and 3-phenylpyrido[3,4-d]pyridazines (XXIV - main reaction product and XXV) under the influence of heating in ethanolic solution of C2H5ONa. Some of N-phenylpiperazinylhydroxyalkyl(alkyl) derivatives of compound XXIV (XXVII, XXVIII) were pharmacologically active.
Asunto(s)
Analgésicos no Narcóticos/síntesis química , Analgésicos no Narcóticos/farmacología , Hipnóticos y Sedantes/síntesis química , Hipnóticos y Sedantes/farmacología , Piridazinas/síntesis química , Piridazinas/farmacología , Piridinas/síntesis química , Piridinas/farmacología , Analgésicos no Narcóticos/toxicidad , Animales , Sinergismo Farmacológico , Hipnóticos y Sedantes/toxicidad , Indicadores y Reactivos , Dosificación Letal Mediana , Ratones , Actividad Motora/efectos de los fármacos , Dimensión del Dolor/efectos de los fármacos , Piridazinas/toxicidad , Piridinas/toxicidad , Tiopental/farmacologíaRESUMEN
The synthesis of tetra(hexa)hydropyrazolo[1,2-a]pyrido[3,4-d]pyridazine derivatives (14-21) and the results of pharmacological screening are described in this paper. All compounds tested were non-toxic and showed a significant analgesic action. The analgesic effects were associated with the suppression of the spontaneous locomotor activity. Furthermore most of the synthesized compounds displayed a weak antimycobacterial action in the preliminary screening.
Asunto(s)
Analgésicos no Narcóticos/síntesis química , Pirazoles/síntesis química , Piridazinas/síntesis química , Analgésicos no Narcóticos/farmacología , Analgésicos no Narcóticos/toxicidad , Animales , Antibacterianos/síntesis química , Antibacterianos/farmacología , Presión Sanguínea/efectos de los fármacos , Dosificación Letal Mediana , Ratones , Pruebas de Sensibilidad Microbiana , Actividad Motora/efectos de los fármacos , Mycobacterium/efectos de los fármacos , Dimensión del Dolor/efectos de los fármacos , Pirazoles/farmacología , Pirazoles/toxicidad , Piridazinas/farmacología , Piridazinas/toxicidad , Ratas , Ratas WistarRESUMEN
A series of aroxyethylamines (1-10) was synthesized and evaluated for hypotensive activity in rats after intravenous and oral administration. The 4 compounds (4, 7, 8 and 10) containing a (2-methoxy)phenylpiperazine moiety displayed hypotensive activity and their affinities for alpha1-, alpha2- and beta1-adrenoreceptors were determined by radioligand binding assays. Compounds 4, 7, 8 and 10 were also tested for their effect on the pressor responses to epinephrine, norepinephrine, methoxamine, tyramine and DMPP. The results suggest that the hypotensive effect of these compounds is related to their alpha- and beta-adrenolytic properties.
Asunto(s)
Antihipertensivos/síntesis química , Antihipertensivos/farmacología , Etilaminas/química , Etilaminas/farmacología , Receptores Adrenérgicos/metabolismo , Administración Oral , Animales , Antihipertensivos/metabolismo , Unión Competitiva/efectos de los fármacos , Presión Sanguínea/efectos de los fármacos , Cromatografía en Capa Delgada , Indicadores y Reactivos , Inyecciones Intravenosas , Cinética , Dosificación Letal Mediana , Espectroscopía de Resonancia Magnética , Masculino , Ratones , Ensayo de Unión Radioligante , Ratas , Ratas Wistar , Receptores Adrenérgicos/efectos de los fármacos , Receptores Adrenérgicos alfa 1/efectos de los fármacos , Receptores Adrenérgicos alfa 1/metabolismo , Receptores Adrenérgicos alfa 2/efectos de los fármacos , Receptores Adrenérgicos alfa 2/metabolismo , Receptores Adrenérgicos beta 1/efectos de los fármacos , Receptores Adrenérgicos beta 1/metabolismo , Relación Estructura-Actividad , Vasoconstrictores/antagonistas & inhibidores , Vasoconstrictores/farmacologíaRESUMEN
Starting from isothiazolopyridine-1,1-dioxide (1), corresponding derivatives of 3-aryl-4-hydroxypyrido[3,2-e]-1,2-thiazine-1,1-dioxide (6) possessing the 3-[4-(substituted-phenyl)piperazinyl]propyl or 3-(4-substituted-piperidinyl)propyl side chain by the nitrogen atom of the thiazine ring were prepared. Under pharmacological central nervous system (CNS) screening in animal models (mice), all of the six pyridothiazines 6 tested exhibited analgesic action as the predominant profile of their activity ('writhing' test 12.5-50 mg/kg). Moreover, the radical scavenging activity against peroxyl radicals of the representative pyridothiazines 6 was evaluated in vitro in water environment and some of them proved to be moderate antioxidants.
Asunto(s)
Analgésicos/síntesis química , Antioxidantes/síntesis química , Sistema Nervioso Central/efectos de los fármacos , Óxidos/síntesis química , Tiazinas/síntesis química , Analgésicos/farmacología , Analgésicos/toxicidad , Animales , Antioxidantes/farmacología , Antioxidantes/toxicidad , Sinergismo Farmacológico , Edema/tratamiento farmacológico , Ratones , Actividad Motora/efectos de los fármacos , Óxidos/farmacología , Óxidos/toxicidad , Dimensión del Dolor , Peróxidos/química , Ratas , Ratas Wistar , Relación Estructura-Actividad , Tiazinas/farmacología , Tiazinas/toxicidad , Tiopental/administración & dosificación , Tiopental/farmacologíaRESUMEN
A series of appropriate aminoisopropanoloxy derivatives of 2-, 3- or 6-xanthone was synthesized and evaluated for anticonvulsant activity in the maximal electroshock seizure (MES) and subcutaneous pentylenetetrazole seizure threshold (ScMet) assays and for neurotoxicity (TOX). The most interesting result was the anticonvulsant activity of (+/-)-3-(2-propylamino)-1- [(2-methyl)-6-xanthonoxy]-2-propanol hydrochloride (10), which displayed anti-MES activity with a protective index (TD50/ED50) of 0.80. Some of the obtained compounds were also tested for their effect on the circulatory system (influence on the non-working heart perfusion, protection against adrenaline induced-arrhythmia) and acute toxicity.
Asunto(s)
Anticonvulsivantes/síntesis química , Anticonvulsivantes/farmacología , Xantinas/síntesis química , Xantinas/farmacología , Animales , Antiarrítmicos/síntesis química , Antiarrítmicos/farmacología , Anticonvulsivantes/toxicidad , Arritmias Cardíacas/inducido químicamente , Arritmias Cardíacas/prevención & control , Circulación Coronaria/efectos de los fármacos , Electrochoque , Epinefrina/farmacología , Hemodinámica/efectos de los fármacos , Dosificación Letal Mediana , Masculino , Ratones , Ratas , Ratas Sprague-Dawley , Ratas Wistar , Convulsiones/prevención & control , Xantinas/toxicidadRESUMEN
The synthesis of 2-(4-substituted)butyl derivatives of 4-alkoxy-2,3-dihydro-6-methyl-1,3-dioxo-1H-pyrrolo[3,4-c]pyridine (10-15) and the results of preliminary pharmacological screening are described in this paper. All the compounds tested showed a strong analgesic action, suppressed spontaneous locomotor activity and prolonged barbiturate sleep. Except 10, all significantly decreased systolic and diastolic blood pressure.
Asunto(s)
Depresores del Sistema Nervioso Central/síntesis química , Depresores del Sistema Nervioso Central/farmacología , Piridinas/química , Piridinas/farmacología , Pirroles/química , Pirroles/farmacología , Analgésicos no Narcóticos/síntesis química , Analgésicos no Narcóticos/farmacología , Analgésicos no Narcóticos/toxicidad , Animales , Barbitúricos/farmacología , Presión Sanguínea/efectos de los fármacos , Depresores del Sistema Nervioso Central/toxicidad , Hipnóticos y Sedantes/farmacología , Dosificación Letal Mediana , Espectroscopía de Resonancia Magnética , Ratones , Actividad Motora/efectos de los fármacos , Dimensión del Dolor/efectos de los fármacos , Piridinas/toxicidad , Pirroles/toxicidad , Ratas , Tiempo de Reacción/efectos de los fármacos , Sueño/efectos de los fármacos , Espectrofotometría Infrarroja , Tiopental/farmacologíaRESUMEN
The effects of vanadium complexes with organic ligands, [VO(phen)2]SO4.3H2O, [VO(bpy)2]SO4.2H2O, and [VOCl2(Hmcp)2H2O], on blood glucose and plasma lipid levels were studied in nondiabetic and streptozotocin-diabetic rats and compared to that of [VO(mal)2] (the reference compound). The present results provide evidence that the compounds examined possess lower toxicity than [VO(mal)2]. One of the compounds examined, viz. [VO(bpy)2]SO4.2H2O, decreases, statistically significantly, the glucose level and a second one, viz. [VOCl2(Hmcp)2H2O], decreases, also significantly, the total cholesterol level.
Asunto(s)
Diabetes Mellitus Experimental/tratamiento farmacológico , Vanadatos/farmacología , Animales , Glucemia/efectos de los fármacos , Presión Sanguínea/efectos de los fármacos , Peso Corporal/efectos de los fármacos , Diabetes Mellitus Experimental/inducido químicamente , Lípidos/sangre , Masculino , Compuestos Organometálicos/farmacología , Compuestos Organometálicos/toxicidad , Ratas , Ratas Wistar , Estreptozocina , Relación Estructura-Actividad , Vanadatos/toxicidadRESUMEN
A series of the new derivatives of imidazolidin-2-one was investigated in order to determine their local anesthetic and antiarrhythmic activity. All compounds tested showed strong local anesthetic properties and variable effects on adrenaline-, aconitine- and barium chloride- induced arrhythmia. The results suggest that the antiarrhythmic properties of these compounds is related to their local anesthetic properties.
Asunto(s)
Anestésicos Locales/síntesis química , Antiarrítmicos/síntesis química , Anestésicos Locales/farmacología , Animales , Antiarrítmicos/farmacología , Arritmias Cardíacas/inducido químicamente , Arritmias Cardíacas/prevención & control , Córnea/efectos de los fármacos , Femenino , Cobayas , Imidazoles/síntesis química , Imidazoles/farmacología , Dosificación Letal Mediana , Masculino , Ratas , Ratas WistarRESUMEN
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.
Asunto(s)
Antiarrítmicos/farmacología , Frecuencia Cardíaca/efectos de los fármacos , Corazón/fisiología , Fenitoína/análogos & derivados , Fenitoína/farmacología , Animales , Antiarrítmicos/química , Circulación Coronaria/efectos de los fármacos , Corazón/efectos de los fármacos , Técnicas In Vitro , Modelos Moleculares , Conformación Molecular , Fenitoína/química , Ratas , Relación Estructura-ActividadRESUMEN
Antiarrhythmic effects and intracellular electrophysiological properties of a new antiarrhythmic compound (-)trans-4-[2-hydroxy-3(N-isopropylamino)-propoxyimino]-cis-car ane (9) were studied in several models of arrhythmia and in isolated guinea-pig myocardial preparations. Compound 9 prevented the aconitine-induced arrhythmia, reversed the ouabin-induced arrhythmia depressed the maximum rate depolarization (Vmax), and shortened the action potential duration (ADP) and the effective refractory period (ERP). The data indicate that compound 9 is an effective antiarrhythmic presumably with a class 1 B mechanism of action.
Asunto(s)
Antiarrítmicos/química , Antiarrítmicos/farmacología , Propranolol/análogos & derivados , Propranolol/farmacología , Terpenos/química , Terpenos/farmacología , Animales , Arritmias Cardíacas/fisiopatología , Arritmias Cardíacas/prevención & control , Femenino , Cobayas , Técnicas In Vitro , Masculino , Propranolol/química , Ratas , Ratas WistarRESUMEN
A series of the derivatives of 1-[2-hydroxy-3-(4-phenyl-1-piperazinyl])propyl]-pyrrolidin-2- one (MG-1) was synthesized and tested for electrocardiographic, antiarrhythmic, and antihypertensive activity as well as for alpha 1- and alpha 2-adrenoceptors binding affinities. Some of the compounds of this series slightly decreased the heart rate, prolonged P-Q, Q-T intervals and QRS complex. Only compound 7 (1-[2-hydroxy-3-(4-phenyl-1-piperazinyl)propyl]-pyrrolidine) possesses potent antiarrhythmic and a slight hypotensive properties, and affinity for alpha 1- and alpha 2-adrenoceptor. The results suggest that the antiarrhythmic and hypotensive effect of compound 7 and MG-1 is related to their adrenolytic properties, and that those properties depend on the presence of a phenylpiperazine moiety.
Asunto(s)
Antagonistas Adrenérgicos alfa/síntesis química , Antagonistas Adrenérgicos alfa/farmacología , Antiarrítmicos/síntesis química , Antiarrítmicos/farmacología , Antihipertensivos/síntesis química , Antihipertensivos/farmacología , Pirrolidinonas/síntesis química , Pirrolidinonas/farmacología , Animales , Ratas , Relación Estructura-ActividadRESUMEN
A series of appropriate aminoalkanolic derivatives of xanthone III-VIII was synthesized and evaluated as potential antiarrhythmic agents. They were also tested for the effect on the cardiovascular system. The structure of the synthesized compounds was verified by IR 1H NMR, 13C NMR and mass spectral data.
Asunto(s)
Antiarrítmicos/síntesis química , Xantenos/síntesis química , Xantonas , Animales , Antiarrítmicos/farmacología , Arritmias Cardíacas/tratamiento farmacológico , Presión Sanguínea/efectos de los fármacos , Electrocardiografía/efectos de los fármacos , Epinefrina , Dosificación Letal Mediana , Espectroscopía de Resonancia Magnética , Masculino , Espectrometría de Masas , Ratones , Ratas , Ratas Wistar , Espectrofotometría Infrarroja , Xantenos/química , Xantenos/farmacologíaRESUMEN
UNLABELLED: The reconstructive processes in a heart infarction pertain also the fibrous tissue sceleton, of which the main element are collagen fibres. The aim of the study was determination of variability of a specific collagen synthesis marker, i.e. the serum aminoterminal type III procollagen peptide (PIIINP) and its correlation with hydroxyproline (HP), hydroxylysin (HL) concentration as well as activity of creatine kinase (CK) and aspartate aminotransferase (AspAT) in serum after heart infarction. The investigations were carried out in 30 patients with a heart infarction with Q wave (group I), in 20 subjects with a heart infarction without Q wave (group II) and in 30 healthy subjects, comprising the C group. All these parameters were determined on the 1st, 2nd, 3rd, 5th and 10th day after onset of infarction. In comparison to the C group, in group I on the 1st day the PIIINP concentration was 3-fold higher and in group II it 2 1/2-fold higher (C = 4.3 +/- 1.8; I = 14.2 +/- 3.9; II = 10.4 +/- 2.0 micrograms/l; p < 0.001). In group I even on the 10th day the concentration did not return to normal values, instead in group II it reached the values x + SD in C group after 5 days. There was no significant correlation between concentration of PIIINP and all other examined parameters stated. Heart infarction with a Q wave caused a relatively highest (% of mean values in C group) increase in CK and AspAT activity, PIIINP held a medial position, while HP and HL the lowest. After infarction without a Q wave the relative elevation of PIIINP concentration was near to the AspAT and HP increase. CONCLUSIONS: 1. the differences of serum PIIINP concentration are probably resulted by the magnitude of heart infarction. 2. During 10 days after the onset of heart infarction the serum concentration of PIIINP does not show any correlation with HP, HL and enzymatic heart infarct markers. 3. The results indirectly show, that the scar formation after heart infarction begins already on the first day.