Deserpidine Antagonism by a Tripeptide, L-Prolyl-L-Leucylglycinamide

Plotnikoff, Nicholas P.; Kastin, A. J.; Anderson, Marydilys S.; Schally, A. V.

doi:10.1159/000122119

Cited by 71 publications

(5 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…One of these was the misconception that increasing the dose of a peptide necessarily increases its effect. We first observed that higher doses of a peptide can result in reduced or even absent effects compared with smaller doses in studies with MIF-1 (Pro-Leu-Gly-NH 2 ) in mice in 1971 (Plotnikoff et al, 1971), in monkeys in 1973 (Plotnikoff et al, 1973), and in human beings in 1974 (Ehrensing and Kastin, 1974), the last results being confirmed in a second clinical study in 1978 . The animal studies involved models of mental depression and Parkinson's disease.…”

mentioning

confidence: 90%

Peptides and Hormesis

Kastin

Pan

2008

Critical Reviews in Toxicology

View full text Add to dashboard Cite

Biology is replete with examples of hormesis, the term introduced and developed by Calabrese. The corresponding concept in the field of peptide research has been characterized as the inverted U-shaped dose-response relationship. The articles by Calabrese in this issue summarize the notable progress occurring in the past three decades. In contrast to the skepticism encountered when we introduced this concept for peptides in the early 1970s, hormesis is now becoming recognized as characteristic of many actions of these small proteins. Calabrese is performing a considerable service by his strong advocacy and promotion of the concept to a more general readership. Hopefully, hormesis will be routinely considered in the design of research projects and the discovery of pharmaceutical agents.

show abstract

mentioning

confidence: 90%

Peptides and Hormesis

Kastin

Pan

2008

Critical Reviews in Toxicology

View full text Add to dashboard Cite

show abstract

“…The reaction conditions and work-up were the same as those described for 8. Recrystallization of the crude product from EtOAc gave 348 mg (50%) of 10: mp 168-170 °C; L-Prolyl-L-leucyl-L-prolinamide (11). The mixed anhydride prepared in THF from 15 (1.9 g, 5.3 mmol), NEt3 (0.53 g, 5.3 mmol), and isobutyl chloroformate (0.72 g, 5.3 mmol) was treated with a solution of L-prolinamide (0.6 g, 5.3 mmol) in THF (10 mL).…”

Section: Methodsmentioning

confidence: 99%

“…In the case of analogue 6 an imino group has been substituted for the methylene group while in compound 7 an additional methylene group has been inserted into the peptide chain. In addition to these modifications, several analogues (8)(9)(10)(11) have been synthesized where either a thiazolidine or pyrrolidine ring system has been incorporated into the glycinamide portion of the molecule.…”

mentioning

confidence: 99%

Study of the structural requirements for Dopa potentiation and oxotremorine antagonism by L-prolyl-L-leucylglycinamide

1978

View full text Add to dashboard Cite

A number of analogs of the tripeptide L-prolyly-L-leucylglycinamide (1) were synthesized and evaluated in the Dopa potentiation and oxotremorine antagonism tests. The replacement of the glycinamide residue with either the glycine methylamide, glycine, aminoacetonitrile, amino-2-propanone, semicarbazide, or beta-alaninamide residues resulted in a loss of activity in both tests. A 1:1 mixture of L-prolyl-L-leucyl-(-)-thiazolidine-2-carboxamide (8) and L-prolyl-L-leucyl-(+)-thiazolidine-2-carboxamide (9) showed marked activity in the Dopa potentiation test but was unable to antagonize the tremors induced by oxotremorine. L-Prolyl-L-leucyl-L-prolinamide (11), on the other hand, was active in the oxotremorine antagonism test but inactive in the Dopa potentiation test. The replacement of the pyrrolidine ring of 1 with either a thiazolidine or cyclopentane ring system caused a loss of activity. The cyclopentanecarboxylic acid analogue 13, however, was found to have moderate activity in the serotonin potentiation test.

show abstract

“…It is active in tests of dopa-potentiation [1,21–23] and oxotremorine antagonism in mice [24–26], and deserpidine antagonism in monkeys as well as mice [27]. It exerts these effects even when given orally to mice and monkeys [27–29], and does not require the presence of the pituitary gland [1,24,28]. MIF-1 is also effective against the neurotoxin MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) that induces many of the clinical symptoms of Parkinson’s disease [30,31].…”

Section: Conceptsmentioning

confidence: 99%

“…Its half-life in human plasma is 5 days although in rat plasma it lasts only a few minutes, like other small peptides including the related Tyr-MIF-1 and endomorphins [109–112]. Moreover, unlike most peptides, many studies have shown that MIF-1 is active orally in rodents [27–29,113] as well as human beings [33,52–54,114]. It is yet to be determined whether MIF-1 is a substrate for oligopeptide transporter (PEPT)-1 in the intestine and PEPT-2 in the choroid plexus, or both in the kidney.…”

Section: Conceptsmentioning

confidence: 99%

Concepts for Biologically Active Peptides

Kastin¹,

Pan²

2010

CPD

View full text Add to dashboard Cite

Here we review a unique aspect of CNS research on biologically active peptides that started against a background of prevalent dogmas but ended by exerting considerable influence on the field. During the course of refuting some doctrines, we introduced several concepts that were unconventional and paradigm-shifting at the time. We showed that (1) hypothalamic peptides can act ‘up’ on the brain as well as ‘down’ on the pituitary, (2) peripheral peptides can affect the brain, (3) peptides can cross the blood-brain barrier, (4) the actions of peptides can persist longer than their half-lives in blood, (5) perinatal administration of peptides can exert actions persisting into adulthood, (6) a single peptide can have more than one action, (7) dose-response relationships of peptides need not be linear, (8) the brain produces antiopiate as well as opiate peptides, (9) there is a selective high affinity endogenous peptide ligand for the mu-opiate receptor, (10) a peptide’s name does not restrict its effects, and (11) astrocytes assume an active role in response to metabolic disturbance and hyperleptinemia. The evolving questions in our laboratories reflect the diligent effort of the neuropeptide community to identify the roles of peptides in the CNS. The next decade is expected to see greater progress in the following areas: (a) interactions of peptides with other molecules in the CNS; (b) peptide involvement in cell-cell interactions; and (c) peptides in neuropsychiatric, autoimmune, and neurodegenerative diseases. The development of peptidomics and gene silencing approaches will expedite the formation of many new concepts in a new era.

show abstract

Deserpidine Antagonism by a Tripeptide, L-Prolyl-L-Leucylglycinamide

Abstract: The tripeptide, L-prolyl-L-leucylglycinamide (PLG) reverses the sedative effects of deserpidine in mice and monkeys treated with pargyline and DOPA. It is effective both orally and when injected intraperitoneally, some of its action possibly being exerted upon the catecholamine system.

Cited by 71 publications

References 0 publications

Peptides and Hormesis

Peptides and Hormesis

Study of the structural requirements for Dopa potentiation and oxotremorine antagonism by L-prolyl-L-leucylglycinamide

Concepts for Biologically Active Peptides

Contact Info

Product

Resources

About