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1.
Hipertens Riesgo Vasc ; 38(3): 133-147, 2021.
Article in Spanish | MEDLINE | ID: mdl-33632659

ABSTRACT

Hypertension (HTN) in pregnancy is defined as systolic blood pressure ≥ 140 and/or diastolic blood pressure ≥ 90 mmHg. Based on the values, it is classified as non-severe (< 160/110 mmHg) and severe (≥ 160/110 mmHg). Before starting treatment in non-severe HTN, white- coat HTN should be ruled out. If outpatient management is possible, pharmacological initiation is suggested with sustained high values, avoiding < 120/80 mmHg. Safe drugs during pregnancy are methyldopa, labetalol, and nifedipine-retard. The use of nifedipine-XL or amlodipine can be considered with a lower level of evidence of safety. Diuretics, atenolol, and other beta-blockers for antihypertensive purposes is not recommended in this period. Renin-angiotensin-aldosterone system inhibitors are strictly contraindicated. In postpartum and breastfeeding, the same therapeutic regimen used during pregnancy can be maintained, trying early withdrawal of methyldopa. During puerperium, amlodipine and enalapril are safe, with minimal excretion in breast milk.


Subject(s)
Hypertension , Nifedipine , Amlodipine/pharmacology , Antihypertensive Agents/pharmacology , Antihypertensive Agents/therapeutic use , Blood Pressure/drug effects , Breast Feeding , Female , Humans , Hypertension/drug therapy , Methyldopa/pharmacology , Methyldopa/therapeutic use , Nifedipine/pharmacology , Postpartum Period , Pregnancy
2.
Fiziol Zh (1994) ; 61(4): 41-7, 2015.
Article in Ukrainian | MEDLINE | ID: mdl-26552304

ABSTRACT

The changes of aromatase and 5α-reductase activities were studied in preoptic area (POA) and medial basal hypothalamus of 10-days-old and sexual behavior in 3-month-old male offsprings of rats exposed daily to noradrenaline antagonist methyldopa (400 mg/kg per os) 30 minutes prior to 1-hour immobilization during the last week of pregnancy (from 15th to 21st day). Prenatal stress caused aromatase activity lowering in the POA of developing brain and feminization (appearance of lordosis) and demasculinization of sexual behavior (prolongation of latent periods to the first mounting and first intromission as well as of the first ejaculation and postejaculation refractory period) in young male offspring. Oral methyldopa used prior to pregnant females stressing prevented early effect of prenatal stress on aromatase activity in the POA and normalized the male sexual behavior in young male rats by shortening both latent period to the first ejaculation and postejaculation refractory period, and an increase of numbers of ejaculation. The data obtained indicate that brain noradrenergic system plays significant role in the mechanisms of metabolic- and behavioral disturbances developing in male rats exposed to prenatal stress.


Subject(s)
Feminization/prevention & control , Hypothalamus/drug effects , Methyldopa/pharmacology , Prenatal Exposure Delayed Effects , Sexual Behavior, Animal/drug effects , Stress, Psychological/prevention & control , Visual Cortex/drug effects , 3-Oxo-5-alpha-Steroid 4-Dehydrogenase/metabolism , Animals , Aromatase/metabolism , Copulation/drug effects , Ejaculation/drug effects , Female , Feminization/enzymology , Feminization/physiopathology , Gestational Age , Hypothalamus/enzymology , Hypothalamus/physiopathology , Immobilization , Male , Maternal Exposure , Pregnancy , Rats , Rats, Wistar , Stress, Psychological/enzymology , Stress, Psychological/physiopathology , Visual Cortex/enzymology , Visual Cortex/physiopathology
3.
Am J Chin Med ; 33(6): 913-21, 2005.
Article in English | MEDLINE | ID: mdl-16355448

ABSTRACT

This research investigated the anti-hypertension effect of the traditional Chinese medicine (TCM) ju-ling-tang (JLT) on an animal model of hypertension induced by unilateral renal artery ligation. In the study of anti-hypertension effects, 60 minutes after oral administration with NG tube feeding of 240 mg/kg JLT, a significant decrease in blood pressure (p < 0.05) was observed and sustained till 120 minutes. In the group given 50 mg/kg alpha-methyldopa orally, the effect was obvious 90 minutes after medication (p < 0.01), and lasted until 240 minutes. In terms of organ pathology, a significant reduction in the extent of induced glomerular sclerosis was observed in rats given 240 mg/kg JLT compared with the control. From these results, we infer that JLT has a beneficial anti-hypertensive effect on renal hypertension.


Subject(s)
Drugs, Chinese Herbal/pharmacology , Hypertension, Renal/drug therapy , Animals , Antihypertensive Agents/pharmacology , Biopsy , Coronary Vessels/drug effects , Coronary Vessels/pathology , Disease Models, Animal , Glomerulosclerosis, Focal Segmental/drug therapy , Kidney/drug effects , Kidney/pathology , Male , Methyldopa/pharmacology , Nifedipine/pharmacology , Rats , Rats, Wistar
4.
J Perinat Med ; 32(4): 315-9, 2004.
Article in English | MEDLINE | ID: mdl-15346815

ABSTRACT

OBJECTIVE: To investigate and compare the direct effects of compounds used in the treatment of hypertensive disease in pregnancy on human umbilical artery resistance in vitro. METHODS: Isometric tension recordings were performed under physiological conditions on human umbilical arterial rings (n=30). The in vitro effects of labetolol, hydralazine, alpha-methyldopa, nifedepine and magnesium sulphate (at concentration ranges from 1 nanomolar to 1 millimolar), and their respective vehicle controls, were measured. Results were expressed as -logEC50 (pD2) and mean maximal inhibition values for each compound. RESULTS: All compounds investigated, except alpha methyldopa, exerted a significant relaxant effect on umbilical arterial tone. Alpha-methyldopa was significantly less potent when compared to all other compounds (mean maximal inhibition value [20.89+/-7.99%] versus all other agents [range 63.15+/-8.70-84.12+/-3.84%] (P<0.01)). The dose response curve of nifedipine yielded a significantly greater PD2 value when compared to that of hydralazine, labetalol, and magnesium sulphate (PD2 value [5.82+/-0.34] versus the above groups [range 3.10+/-0.09-3.52+/-0.14] (P <0.01)). CONCLUSION: These findings demonstrate that agents commonly used for the treatment of hypertensive disease in pregnancy, excluding alpha-methyldopa, have significant direct effects on the feto-placental circulation. These results suggest that alpha-methyldopa administration during pregnancy is less likely to produce significant direct effects on fetal vasculature then other agents used.


Subject(s)
Antihypertensive Agents/pharmacology , Fetus/blood supply , Placenta/blood supply , Pre-Eclampsia/physiopathology , Umbilical Arteries/physiology , Adult , Antihypertensive Agents/administration & dosage , Antihypertensive Agents/therapeutic use , Dose-Response Relationship, Drug , Female , Humans , Hydralazine/administration & dosage , Hydralazine/pharmacology , Hydralazine/therapeutic use , Labetalol/administration & dosage , Labetalol/pharmacology , Labetalol/therapeutic use , Magnesium Sulfate/administration & dosage , Magnesium Sulfate/pharmacology , Magnesium Sulfate/therapeutic use , Methyldopa/administration & dosage , Methyldopa/pharmacology , Methyldopa/therapeutic use , Nifedipine/administration & dosage , Nifedipine/pharmacology , Nifedipine/therapeutic use , Pre-Eclampsia/drug therapy , Pregnancy , Regional Blood Flow , Umbilical Arteries/drug effects , Vascular Resistance/drug effects
5.
Pharmacol Res ; 48(1): 61-7, 2003 Jul.
Article in English | MEDLINE | ID: mdl-12770516

ABSTRACT

Pharmacokinetics of methyldopa (MD) and the effect on the dopaminergic metabolism was studied in anesthetized sham-operated (SO) and sinoaortic-denervated (SAD) rats by using the microdialysis technique. A concentric microdialysis probe was placed in the striatum or in the posterior hypothalamus. Levels of MD, homovanillic acid (HVA), and 3,4-dihydroxyphenylacetic acid (DOPAC) were measured by high pressure liquid chromatography coupled to electrochemical detection (HPLC-EC). Following the i.p. administration of MD (50 mg x kg(-1), i.p.), striatal dialysates showed that this drug rapidly reaches the brain. However, in SAD rats the MD levels of dialysates were lower and decreased more rapidly compared to SO rats. On the other hand, dialysates of posterior hypothalamus showed that in SAD animals the accumulation of MD was significantly greater than in SO rats.MD does not significantly reduce the striatal production of dopaminergic metabolite DOPAC in both groups of rats. The drug also induces a decrease of DOPAC levels in hypothalamic dialysates of SO and SAD animals. On the other hand, a no significative decay of HVA levels was seen in the striatal dialysate of both groups of experimental animals. In conclusion, this study by using a microdialysis technique shows that MD has different kinetic profiles in dialysates from posterior hypothalamus and striatum of SO and SAD rats at a dose that alters dopaminergic metabolism.


Subject(s)
Adrenergic alpha-Agonists/pharmacokinetics , Brain Chemistry/drug effects , Brain/metabolism , Dopamine/metabolism , Methyldopa/pharmacokinetics , 3,4-Dihydroxyphenylacetic Acid/metabolism , Adrenergic alpha-Agonists/pharmacology , Animals , Brain Chemistry/physiology , Corpus Striatum/metabolism , Denervation/methods , Homovanillic Acid/metabolism , Hypothalamus/metabolism , Male , Methyldopa/pharmacology , Microdialysis , Pressoreceptors , Rats , Rats, Wistar
6.
Pharmacol Res ; 44(5): 377-83, 2001 Nov.
Article in English | MEDLINE | ID: mdl-11712868

ABSTRACT

A pharmacokinetic-pharmacodynamic study of methyldopa (MD) was made in anesthetized sham operated (SO) and aortic coarctated (ACo) rats by using a vascular shunt probe for arterial microdialysis and simultaneous blood pressure recording. Anesthetized Wistar rats were used 7 days after aortic coarctation or sham operation. A vascular shunt probe was inserted into the carotid artery and a concentric probe was placed into the striatum or posterior hypothalamus. MD and 3,4-dihydroxyphenylacetic acid (DOPAC) were determined in the dialysates by HPLC-EC. MD (50 mg kg(-1)i.p.) induced an increase of heart rate in SO (Delta HR: 108 +/- 22 bpm, n= 6) and in ACo rats (Delta HR: 55 +/- 10 bpm, n= 6, P< 0.05, one way ANOVA). Moreover, MD also reduced the mean arterial pressure (MAP) of SO rats (Delta MAP: -10 +/- 4 mmHg, n= 6) and ACo animals (Delta MAP: -51 +/- 9 mmHg, n= 6, P< 0.05, one way ANOVA). Analysis of the arterial blood dialysates showed a lower half-life of MD in ACo rats (t(1/2): 1.5 +/- 0.3 h, n= 6, P< 0.05, 't' test) than in SO rats (t(1/2): 3.7 +/- 1.0 h, n= 6). A low accumulation and a fast decay of striatal MD levels were seen in ACo rats. However, peak levels of drug were greater in the hypothalamic dialysates of ACo rats than in SO animals samples. On the other hand, MD also induced an increase of DOPAC levels in the hypothalamic dialysates of ACo rats. In conclusion, the aortic coarctation modifies the pharmacokinetic and cardiovascular effect of MD in the rat. The action of this drug on dopaminergic neurotransmission is also altered in the ACo animals.


Subject(s)
Antihypertensive Agents/pharmacokinetics , Aortic Coarctation/metabolism , Methyldopa/pharmacokinetics , Microdialysis , 3,4-Dihydroxyphenylacetic Acid/metabolism , Animals , Antihypertensive Agents/pharmacology , Aortic Coarctation/physiopathology , Blood Pressure/drug effects , Corpus Striatum/drug effects , Corpus Striatum/metabolism , Dialysis Solutions/pharmacokinetics , Hypothalamus/drug effects , Hypothalamus/metabolism , Methyldopa/administration & dosage , Methyldopa/pharmacology , Microdialysis/methods , Rats , Rats, Wistar
7.
Eksp Klin Farmakol ; 56(5): 38-41, 1993.
Article in Russian | MEDLINE | ID: mdl-8312808

ABSTRACT

The paper deals with some aspects of the effects produced by dopegite on the pharmacokinetics and pharmacodynamics of foridone from a group of calcium antagonists. Nineteen patients with essential hypertension received a single doses of foridone of 40 mg, then its course therapy in a dose of 90 mg/day for 2 weeks, then it was supplemented with dopegite in a dose of 750 mg/day for 2 weeks too. Supplementation of dopegite caused statistically significant changes as higher plasma concentrations of foridone and increased concentration-time curve areas, decreased total peripheral resistance and regional, and a lower spasm index. Dopegite can be used to enhance the antihypertensive effect of foridone.


Subject(s)
Calcium Channel Blockers/pharmacokinetics , Methyldopa/pharmacokinetics , Nifedipine/analogs & derivatives , Adult , Calcium Channel Blockers/pharmacology , Calcium Channel Blockers/therapeutic use , Depression, Chemical , Dose-Response Relationship, Drug , Drug Interactions , Drug Therapy, Combination , Female , Hemodynamics/drug effects , Humans , Hypertension/blood , Hypertension/drug therapy , Hypertension/physiopathology , Male , Methyldopa/pharmacology , Methyldopa/therapeutic use , Middle Aged , Nifedipine/pharmacokinetics , Nifedipine/pharmacology , Nifedipine/therapeutic use , Oxidation-Reduction/drug effects , Time Factors
8.
Gynecol Obstet Invest ; 33(4): 213-5, 1992.
Article in English | MEDLINE | ID: mdl-1505808

ABSTRACT

To determine the possible effects of alpha-methyldopa on the motility of human umbilical artery, a total of 53 arterial segments were perfused with different concentrations of the drug as follows: 38 segments with 125, 250 and 500 ng/ml of the drug, 9 segments with 500 ng/ml alpha-methyldopa in combination with 10(-7) M yohimbine, and 6 segments with 10(-7) M yohimbine alone. alpha-Methyldopa had a vasoconstrictor effect at all doses employed, with a clear dose-effect correlation (p less than 0.01). The vasoconstrictor effect of 500 ng/ml alpha-methyldopa was fully inhibited in the presence of 10(-7) M yohimbine. These results suggest that alpha 2-adrenergic receptors are present in the umbilical circulation and that alpha-methyldopa may play a role in the control of this circulation.


Subject(s)
Blood Circulation/drug effects , Hemodynamics/drug effects , Methyldopa/pharmacology , Umbilical Arteries/drug effects , Drug Evaluation, Preclinical , Drug Therapy, Combination , Humans , Infant, Newborn , Methyldopa/administration & dosage , Yohimbine/administration & dosage , Yohimbine/pharmacology
9.
Ann Plast Surg ; 23(2): 117-22, 1989 Aug.
Article in English | MEDLINE | ID: mdl-2505660

ABSTRACT

There is a myriad of research in the pharmacological manipulation of skin flap survival. However, skepticism exists as to whether any of these drugs is clinically useful. We evaluated the efficacy of five categories of agents in improving skin flap survival in five different rat flap models. Diltiazem, isoxsuprine hydrochloride, nitroglycerin, prazosin hydrochloride (two doses), and methyldopa were compared in a double-blind, randomized fashion. Their benefits were assessed in a musculocutaneous flap, axial flap, and three types of random flaps. The "best" drug was determined to be nitroglycerin. Its efficacy was verified in a primate model.


Subject(s)
Graft Survival/drug effects , Surgical Flaps , Animals , Diltiazem/pharmacology , Dose-Response Relationship, Drug , Double-Blind Method , Drug Evaluation, Preclinical , Isoxsuprine/pharmacology , Macaca nemestrina , Male , Methyldopa/pharmacology , Nitroglycerin/pharmacology , Prazosin/pharmacology , Rats
10.
Eur J Pharmacol ; 164(3): 531-8, 1989 May 30.
Article in English | MEDLINE | ID: mdl-2767124

ABSTRACT

Blood pressure (BP), hypothalamic tissue concentrations and the in vivo overflow of endogenous and alpha-methylated catecholamines were measured in urethane anaesthetised rats after alpha-methylDOPA (mDOPA) administration (200 mg/kg i.p.). Four hours after mDOPA, BP fell to its lowest value, 60% of control, and slowly returned towards control levels by 24 h. This was closely correlated with the evoked overflow of alpha-methylnoradrenaline (mNA, r = 0.9) and noradrenaline (NA, r = 0.7) but not dopamine (DA) or alpha-methyldopamine (mDA). However, the tissue content of mNA rose much more gradually and was not maximal until after 12 h while mDA content followed the development of the hypotension. The results provide direct evidence for a false transmitter role for mNA in the brain, and suggest that the release of newly synthesised mNA is responsible for the hypotensive effect of mDOPA. Differences in the time course of overflow and storage of NA and mNA suggest the presence of separate transmitter storage and releasable pools.


Subject(s)
Biogenic Amines/metabolism , Blood Pressure/drug effects , Methyldopa/pharmacology , Animals , Catecholamines/metabolism , Dialysis , Hypothalamus/drug effects , Hypothalamus/metabolism , Male , Potassium/pharmacology , Rats , Rats, Inbred SHR
11.
Brain Res ; 444(2): 380-2, 1988 Mar 22.
Article in English | MEDLINE | ID: mdl-3359304

ABSTRACT

This report shows the existence of endogenous p-tyramine in the nerve cord and some organs of the lobster. Their concentrations are lower than those of dopamine or 5-hydroxytryptamine. The nerve cord levels of m-tyramine, beta-phenylethylamine and tryptamine are much lower than those of the phenolic or catecholic amines. The finding that the administration of an aromatic-L-amino acid decarboxylase inhibitor leads to a decrease of p-tyramine gives further evidence that this amine is synthesized from p-tyrosine, which is also found in high concentrations in the lobster nerve cord. The widespread distribution of p-tyramine in the nervous system and peripheral tissues of the lobster suggests that this amine may have additional roles rather than functioning only as a precursor of p-octopamine.


Subject(s)
Biogenic Amines/metabolism , Nephropidae/metabolism , Nervous System/metabolism , Tyramine/metabolism , Animals , Chromatography, High Pressure Liquid , Female , Male , Methyldopa/analogs & derivatives , Methyldopa/pharmacology , Osmolar Concentration , Tissue Distribution
12.
Circ Res ; 62(2): 384-94, 1988 Feb.
Article in English | MEDLINE | ID: mdl-2962785

ABSTRACT

To evaluate the role of extra-atrial atrial natriuretic peptide (ANP) in volume and blood pressure regulation, the plasma, atrial, ventricular, and hypothalamic levels of immunoreactive atrial natriuretic peptide (IR-ANP) were measured simultaneously in the spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY) at the ages of 2, 6, and 12 months. Plasma IR-ANP in the 12-month-old, conscious SHR was significantly higher than that of the WKY (300 +/- 18 versus 200 +/- 20 pg/ml, p less than 0.05, n = 9), while no differences in plasma IR-ANP levels were found between the strains in younger rats. Acute volume expansion with saline (1.1 ml/100 g body wt) in hypertensive as well as in normotensive rats resulted in marked increases in right atrial pressure and plasma IR-ANP concentration. The older SHR had attenuated ANP release to volume loading as shown by the shift of the ANP versus right atrial pressure curve to the right. Right auricular IR-ANP concentration decreased, while that of left auricle increased with increasing age in both strains. No substantial differences were noted in auricular ANP concentration between SHR and WKY. However, the total atrial IR-ANP content (micrograms/atria) was consistently lower in SHR compared with WKY. In both ventricles, IR-ANP concentrations and contents increased with increasing age in WKY and SHR, but the ventricular levels of ANP were reduced in ventricles of the SHR heart compared with normotensive controls. The depletion of total ventricular IR-ANP was greatest in SHR with greatest ventricular hypertrophy and coincided with the attenuated ANP release to acute volume load. The increase of left but not right ventricular weight occurring secondary to 6 weeks minoxidil treatment was accompanied by higher ANP concentration in both strains. In contrast to the ventricles, the hypothalamic IR-ANP concentration was significantly increased in SHR compared with that of WKY and decreased in both strains after 6 weeks' treatment with antihypertensive drugs. Thus, ventricular and hypothalamic, as well as atrial, ANP respond to increased pressure overload in genetically hypertensive rats. Our results suggest that chronic stimulation of ANP release from ventricles is associated with depleted stores of ANP from both ventricles and reduced response to acute volume load. Our findings that ventricular ANP increased with increasing weight and in response to a hypertrophic stimulus in WKY and was decreased in SHR with severe ventricular hypertrophy suggest that ANP may locally have an inhibitory effect on the development of cardiac hypertrophy.


Subject(s)
Atrial Natriuretic Factor/analysis , Hypertension/metabolism , Hypothalamus/analysis , Myocardium/analysis , Animals , Atrial Natriuretic Factor/biosynthesis , Atrial Natriuretic Factor/immunology , Blood Pressure/drug effects , Body Weight/drug effects , Cardiomegaly/metabolism , Heart Rate/drug effects , Kidney/drug effects , Male , Methyldopa/pharmacology , Minoxidil/pharmacology , Organ Size/drug effects , Rats , Rats, Inbred SHR , Rats, Inbred WKY
13.
Clin Exp Hypertens A ; 9(12): 2061-73, 1987.
Article in English | MEDLINE | ID: mdl-3436081

ABSTRACT

To elucidate the role of circulating hypertensive factors in the spontaneously hypertensive rat and the effects of antihypertensive treatment on the circulating hypertensive factor, cross circulation was performed in 54 couples of spontaneously hypertensive and normotensive rats. In normotensive rats cross-circulated with untreated spontaneously hypertensive rats mean arterial pressure increased by 20.9 +/- 12.2 mm Hg (p less than 0.01). Increases in mean arterial pressure were also obtained by cross-circulation with spontaneously hypertensive rats pretreated with propranolol, furosemide, and nifedipine. Mean arterial pressure was not changed by cross circulation after pretreatment of the spontaneously hypertensive rats with alpha methyldopa. It is concluded that in this strain of spontaneously hypertensive rats a circulating hypertensive factor exists, the secretion of which can be suppressed by the centrally acting drug, alpha methyldopa. Therefore either the central nervous system may take part in the regulation of the factor or the factor may be synthetized in the central nervous system.


Subject(s)
Antihypertensive Agents/pharmacology , Hypertension/blood , Animals , Cross Circulation , Furosemide/pharmacology , Hypertension/drug therapy , Male , Methyldopa/pharmacology , Nifedipine/pharmacology , Propranolol/pharmacology , Rats , Rats, Inbred SHR
14.
J Pineal Res ; 2(2): 169-76, 1985.
Article in English | MEDLINE | ID: mdl-2420961

ABSTRACT

The simultaneous effect of alpha-monofluoromethyldopa (MFMD) on the synthesis of rat brain indolealkylamines has been investigated both in the daytime and in the dark phase. The effect on serum melatonin concentration has also been determined in the dark period. MFMD inhibits 5-hydroxytryptophan decarboxylase in the pineal gland, hypothalamus, and the cerebral cortex. Simultaneous measurement of 5-hydroxytryptophan (5-HTP), 5-hydroxytryptamine (5-HT), and 5-hydroxyindoleacetic acid (5-HIAA) levels in the three brain areas revealed that MFMD caused large increases in pineal 5-HTP concentrations and substantial decreases in pineal 5-HT and 5-HIAA both in the light and dark phases; a significant decrease in daytime hypothalamic 5-HT content after 7-h pretreatment; and a large increase in dark-phase cortical 5-HT concentration after 4-h pretreatment. Serum melatonin levels were also reduced by the action of MFMD in the dark period. The evidence suggests that differences occur in the rate-limiting steps in the indolealkylamine biosynthesis in the three brain areas.


Subject(s)
Brain/metabolism , Indoles/biosynthesis , Melatonin/blood , Methyldopa/analogs & derivatives , 5-Hydroxytryptophan/analysis , Animals , Aromatic-L-Amino-Acid Decarboxylases/metabolism , Cerebral Cortex/metabolism , Hydroxyindoleacetic Acid/analysis , Hypothalamus/metabolism , Male , Methyldopa/pharmacology , Pineal Gland/metabolism , Rats , Rats, Inbred Strains , Serotonin/analysis
15.
Hypertension ; 6(5 Pt 2): II87-93, 1984.
Article in English | MEDLINE | ID: mdl-6150004

ABSTRACT

This symposium reviewed the fundamental principles, pharmacology, and clinical pharmacology of central alpha-adrenergic blood pressure regulating mechanisms. Fundamental principles Arterial baro- and chemoreceptor signals reach the nucleus of the tractus solitarius (NTS) via vagal and glossopharyngeal afferents. The NTS communicates with sympathetic preganglionic neurons in the spinal cord via centers and tracts in the medulla, pons, and hypothalamus that include an alpha-adrenergic inhibitory network. Descending tracts emphasized in this symposium originate in the C-1 epinephrine cells of the medulla, B-1 and B-3 serotonin cells of the medulla, and A-5 norepinephrine cells of the pons. Transmitters involved are norepinephrine, epinephrine, serotonin, glutamate, and gamma-aminobutyric acid (GABA). Catecholamine enzymes share protein domains in their primary structures and may be coded by linked or single genes. New methods of purifying and locating alpha- and beta-receptors have been developed. Pharmacology Methyldopa, clonidine, and clonidine-like drugs lower blood pressure by stimulating postsynaptic alpha 2-receptors in a brain stem inhibitory network, which down-regulates these receptors. Alpha 1-receptors were found to be higher in normotensive than in hypertensive rats and were increased in the latter by methyldopa administration. Alpha 2-receptors were found to differ in various tissues, which permits the development of highly selective agonists and antagonists. Although alpha-methylnorepinephrine is probably the principal metabolite of methyldopa, alpha-methylepinephrine and alpha-methyldopamine may also contribute. The site of action usually is identified as the NTS. Possible roles for the descending tracts were suggested. Clinical pharmacology Methyldopa, clonidine, guanfacine, and related drugs lower blood pressure principally by CNS mechanisms but peripheral actions may also contribute.(ABSTRACT TRUNCATED AT 250 WORDS)


Subject(s)
Blood Pressure , Receptors, Adrenergic, alpha/physiology , Afferent Pathways/physiology , Animals , Antihypertensive Agents/adverse effects , Blood Pressure/drug effects , Brain/physiology , Clonidine/pharmacology , Epinephrine/physiology , Glossopharyngeal Nerve/physiology , Glutamates/physiology , Glutamic Acid , Guanfacine , Guanidines/pharmacology , Humans , Hypothalamus/physiology , Medulla Oblongata/physiology , Methyldopa/metabolism , Methyldopa/pharmacology , Norepinephrine/metabolism , Norepinephrine/physiology , Phenylacetates/pharmacology , Pons/physiology , Pressoreceptors/physiology , Serotonin/physiology , Spinal Cord/physiology , Substance Withdrawal Syndrome , Vagus Nerve/physiology , gamma-Aminobutyric Acid/physiology
16.
Brain Res Bull ; 13(2): 257-62, 1984 Aug.
Article in English | MEDLINE | ID: mdl-6498532

ABSTRACT

The formation of 3H-acetylcholine was measured in several brain regions of spontaneously hypertensive (SH) rats following intracerebroventricular injection of 3H-choline. Endogenous acetylcholine (ACh) also was measured and specific activity-time curves for brain ACh generated for control SH rats and for SH rats pretreated with methyldopa (100-200 mg/kg, IV). The relative turnover rates for ACh in several brain regions was estimated from the specific activity-time curves. The turnover rates of ACh in rostral hypothalamus, caudal hypothalamus, medulla oblongata and pons were reduced by 34-54%. Apparently synthesis was inhibited also since methyldopa produced relatively little effect on ACh levels. More rostral brain regions, thalamus-septum, midbrain and striatum, were not significantly affected by methyldopa. Methyldopa also reduced arterial pressure by 53/28 mmHg. The ability of methyldopa to inhibit the function of cholinergic neurons in selective brain regions may be responsible for its common "anticholinergic" side effects. Since centrally-acting anticholinergic drugs reduce arterial pressure in SH rats, it is possible that inhibition of brain ACh synthesis by methyldopa also may contribute to its antihypertensive action in experimental genetic hypertension.


Subject(s)
Acetylcholine/biosynthesis , Methyldopa/pharmacology , Animals , Choline/metabolism , Corpus Striatum/metabolism , Hypothalamus/metabolism , Male , Medulla Oblongata/metabolism , Mesencephalon/metabolism , Pons/metabolism , Rats , Rats, Inbred SHR , Septum Pellucidum/metabolism , Thalamus/metabolism
17.
Adv Alcohol Subst Abuse ; 3(3): 19-39, 1984.
Article in English | MEDLINE | ID: mdl-6388273

ABSTRACT

The efficacy of clonidine in the management of opiate withdrawal states has improved and refined the medical approach to this condition. In addition, the use of clonidine for opiate detoxification paves the way for naltrexone maintenance. Naltrexone, by providing chronic opiate receptor blockade, prevents opiate intoxication and subsequent readdiction in recovered addicts. The sequential use of clonidine and naltrexone, in conjunction with drug rehabilitation, appears to represent a viable and effective treatment for opiate addiction in motivated patients. The development of clonidine and naltrexone as treatment agents for opiate addiction also demonstrates that neurobiological advances can be translated into new and effective clinical approaches. This paper summarizes some of our experiences with the clonidine/naltrexone approach in motivated opiate addicts.


Subject(s)
Clonidine/therapeutic use , Naloxone/analogs & derivatives , Naltrexone/therapeutic use , Opioid-Related Disorders/rehabilitation , Substance Withdrawal Syndrome/prevention & control , Adult , Baclofen/pharmacology , Baclofen/therapeutic use , Clonidine/administration & dosage , Clonidine/analogs & derivatives , Clonidine/pharmacology , Drug Therapy, Combination , Electric Stimulation Therapy , Endorphins/physiology , Ethanol/pharmacology , Ethanol/therapeutic use , Female , Humans , Locus Coeruleus/drug effects , Locus Coeruleus/physiology , Male , Methyldopa/pharmacology , Methyldopa/therapeutic use , Naltrexone/administration & dosage , Naltrexone/pharmacology , Opioid-Related Disorders/drug therapy , Opioid-Related Disorders/physiopathology
18.
Acta Physiol Hung ; 61(1-2): 99-103, 1983.
Article in English | MEDLINE | ID: mdl-6314745

ABSTRACT

Pituitary-adrenocortical function and the changes of hypothalamic catecholamine content were studied following alpha-methyl-dopa treatment in rats. After three-day administration of alpha-methyl-dopa the plasma corticosterone concentration increased significantly and at the same time ether stress failed to elicit a pituitary-adrenocortical response. Moreover, the alpha-methyl-dopa pretreatment prevented the facilitatory effect of physostigmine on pituitary-adrenocortical activation. As the result of alpha-methyl-dopa treatment the norepinephrine content decreased significantly and the amount of compounds measured as dopamine (dopamine, alpha-methyl-dopamine and alpha-methyl-dopa) increased in the hypothalamus. It is concluded that the impaired metabolism of catecholamines may inhibit the pituitary-adrenocortical activation to stimulation, and that not only norepinephrine and dopamine, but other phenylalanine derivatives and alpha-methyl-dopa may also influence the responsiveness of pituitary-adrenocortical function.


Subject(s)
Adrenocorticotropic Hormone/metabolism , Methyldopa/pharmacology , Parasympathomimetics/pharmacology , Pituitary-Adrenal System/drug effects , Stress, Physiological/metabolism , Animals , Corticosterone/blood , Corticotropin-Releasing Hormone/metabolism , Dopamine/physiology , Female , Hypothalamo-Hypophyseal System/drug effects , Hypothalamus/analysis , Hypothalamus/drug effects , Male , Norepinephrine/analysis , Physostigmine/pharmacology , Rats
20.
Experientia ; 37(1): 52-3, 1981 Jan 15.
Article in English | MEDLINE | ID: mdl-6781929

ABSTRACT

In reserpinized mice the occurrence of goldthioglucose hypothalamic lesions was significantly lower than in control mice. Some protection was also conferred by serotonin-receptor blockers and by treatment with nialamide + DL-alpha-methyldopa, but the protective effect of reserpine was not reversed by serotonergic and dopaminergic agonists, alone or in combination, nor by insulin.


Subject(s)
Aurothioglucose/pharmacology , Gold/pharmacology , Hypothalamus, Middle/drug effects , Hypothalamus/drug effects , Reserpine/pharmacology , Animals , Cinanserin/analogs & derivatives , Cinanserin/pharmacology , Dose-Response Relationship, Drug , Drug Interactions , Methiothepin/pharmacology , Methyldopa/pharmacology , Mice , Nialamide/pharmacology , Serotonin Antagonists/pharmacology
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