Amines in Experimental Hypertensions

Ohler, E. A.; Wakerlin, G. E.

doi:10.1161/01.res.1.2.122

Cited by 7 publications

(5 citation statements)

References 7 publications

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“…Another possible explanation implies that APLs stimulate the immune system in order to regulate the MS related T-cells [23]. Two phase II trials using an APL designed based on the human immunodominant MBP [83][84][85][86][87][88][89][90][91][92][93][94][95][96][97][98][99] peptide have been reported [24,25]. Both were stopped prematurely due to hypersensitivity reactions in one and disease exacerbation in the other.…”

Section: Linear and Cyclic Apls Against Msmentioning

confidence: 99%

“…In an attempt to correlate the antagonistic activity of linear APLs of MBP [87][88][89][90][91][92][93][94][95][96][97][98][99] with their conformation, full molecular dynamics studies of their complexes with HLA-DR2b in aqueous solvent have been performed [36]. It was found that once bound to the MHC, significant changes occur in the orientation of the amino acids that serve as TCR anchors, compared to their conformation in solution.…”

Section: Linear and Cyclic Apls Against Msmentioning

confidence: 99%

“…Over the past years the drug industry has been making significant efforts on developing and producing antihypertensive drugs based on renin inhibition. Many potential drug agents have been developed by the pharmaceutical industry, the first class of which were peptidic analogues in the early 1950's, like pepstatin [99]. In the late 1980's tetrapeptide-like agents were developed, in terms of molecular weight and pharmacophore groups, but presented low bioavailability and short duration of action.…”

Section: Renin Inhibitors a Rough Journeymentioning

confidence: 99%

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Peptides as Therapeutic Agents or Drug Leads for Autoimmune, Hormone Dependent and Cardiovascular Diseases

Mantzourani¹,

Laimou²,

Matsoukas³

et al. 2008

AIAAMC

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Peptides regulate most physiological processes, mainly by binding to specific receptors located on the cell surface and inducing a series of signals, neurotransmissions or the release of growth factors. There has been a rapid expansion in the use of peptides as therapeutic agents after the 1960s, but a series of unfortunate side effects present in Phase I and II clinical studies combined with their low bioavailability, led to the introduction of the idea of peptidomimetics as alternative compounds that mimic the biological activity of peptides, while offering the advantages of increased bioavailability, biostability, bioefficiency, and bioselectivity. Since then new peptides with promising in vitro results, involving the monoclonal antibody expansion, as well as the newly launched research field for novel formulations for increasing peptides' bioavailability, redirected the interest on the peptide market. In this report we will highlight three areas where the use of peptides has shown promising results, with products that are either currently used as drugs or included into Phase III clinical studies.

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Section: Linear and Cyclic Apls Against Msmentioning

confidence: 99%

Section: Linear and Cyclic Apls Against Msmentioning

confidence: 99%

Section: Renin Inhibitors a Rough Journeymentioning

confidence: 99%

See 1 more Smart Citation

Peptides as Therapeutic Agents or Drug Leads for Autoimmune, Hormone Dependent and Cardiovascular Diseases

Mantzourani¹,

Laimou²,

Matsoukas³

et al. 2008

AIAAMC

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“…Parahydroxyamphetamine (HANNA, 1960;SCHMITT and SCHtvIlTT, 1970;VALETTE et al, 1971), and phydroxynorephedrine (SCHl\lITT and SCHMITT, 1970;VALETTE et al, 1971) have been shown to have pressor effects in several animal species. However, p-hydroxyamphetamine has antihypertensive effects in addition to pressor effect under certain conditions (OHLER and WAKERLIN, 1953). It may be suggested that the delayed antihypertensive effect might be due to the depletion of NA and incorporation of phydroxynorephedrine into peripher al or central NA neurons.…”

Section: :) the Pressor Responsementioning

confidence: 99%

General Pharmacology of Amphetamine-Like Drugs

Änggård¹,

Lewander²,

Gunne³

1973

Drug Addiction II

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Amphetamine and related central stimulant drugs are derivatives of ß-phenylethylamine (Table 1) and are thus relatively simple organic bases. The general ßphenylethylamine skeleton is one which amphetamine shares with the neurotransmitters noradrenaline, adrenaline, and dopamine. Phenylethylamine itselfhas central stimulant properties, but has an extremely short half-life in the body due to rapid metabolism by monoamine oxidase (MAO). Amphetamine has, due to steric hindrance by the ex-methyl group, much less affinity for MAO and therefore has a longer half-Iife.Most amphetamines have cardiovascular, psychomotor stimulant, hyperthermic, and anorexigenic actions. All of the structural features of amphetamine are important far its spectrum of pharmacologic activity. Any alteration may enhance, diminish, or attenuate one or several components in the actions of the parent drug. (1) Substitution of the phenyl ring, (2) alteration of the length of the side chain, (3) substitution on the primary nitrogen group, (4) substitution of the ex-and ß-carbon atoms, and (5) their absolute configuration have been studied and will be briefly discussed here. For a more thorough review on the subject the reader is referred to the papers by BIEL (1970), vANRossuM and SIMONS (1969) and VREE (1973. The effect of ring and side-chain substitution on distribution and elimination of the amphetamines has been discussed by BECKETT and BROOKES (1970). recently reviewed the biochemical pharmacology of the amphetamines. The metabolism and disposition of methylphenidate were reported by F ARAJ et al.

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“…This possibility is given credence by evidence of impaired adrenergic neuron function after moderate to large doses of amphetamine (1). Also, p-hydroxyamphetamine (PHA), the intermediary metabolite in the conversion of amphetamine to PHN, has similarly been shown to suppress reflex sympathetic function in normotensive human (4) and to lower the blood pressure (BP) in hypertensive dogs (5).…”

Section: Introductionmentioning

confidence: 99%

Effects of a False Neurotransmitter, p-Hydroxynorephedrine, on the Function of Adrenergic Neurons in Hypertensive Patients

Rangno¹,

Kaufmann²,

Cavanaugh³

et al. 1973

J. Clin. Invest.

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A D S T R A C T Previous studies have shown that amphetamine and p-hydroxyamphetamine impair adrenergic transmission, and it has been suggested that this effect is mediated by an active metabolite, p-hydroxynorephedrine (PHN). Studies in experimental animals have shown that PHN can deplete and substitute for norepinephrine (NE) in the transmitter pool, thus meeting the criteria of a false neurotransmitter.The pharmacologic effects of PHN on adrenergic function and NE synthesis were studied in eight hypertensive patients and compared with placebo. Mean erect and supine blood pressure (BP) decreased 22/14 and 9/6 mm Hg, respectively, during PHN 600 mg daily. The post-Valsalva diastolic overshoot was abolished. The pressor sensitivity to tyramine decreased whereas the pressor response to NE was enhanced. A mild natriuresis occurred. The 24 h urinary excretion of catecholamines and catecholamine metabolites during the administration of PHN compared with placebo changed as follows: vanillylmandelic acid (VMA), 42% decrease; NE, 42% decrease; normetanephrine (NM), 400% increase; metanephrine, unchanged; dopamine, 40% decrease; while homovanillic acid was unchanged. The sum of VMA, NE, and NM decreased 23%. The posttreatment urinary excretion of PHN was biexponential with first and second phase half-lives of 13 and 55 h, respectively.

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Amines in Experimental Hypertensions

Cited by 7 publications

References 7 publications

Peptides as Therapeutic Agents or Drug Leads for Autoimmune, Hormone Dependent and Cardiovascular Diseases

Peptides as Therapeutic Agents or Drug Leads for Autoimmune, Hormone Dependent and Cardiovascular Diseases

General Pharmacology of Amphetamine-Like Drugs

Effects of a False Neurotransmitter, p-Hydroxynorephedrine, on the Function of Adrenergic Neurons in Hypertensive Patients

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