Potential Psychotropic Activity of Phlebotropic Drugs: Weak Interactions with Brain Benzodiazepine Receptors

1994 ◽  
Vol 9 (1) ◽  
pp. 32-36 ◽  
Author(s):  
W. Blätter ◽  
P. Schoch
Keyword(s):  
Weak Interactions ◽  
Benzodiazepine Receptors ◽  
Positive Influence ◽  
Binding Activity ◽  
Psychotropic Activity ◽  
Venous Disease ◽  
Receptor Binding Activity ◽  
Psychometric Studies ◽  
Organic Disorder

Background: Epidemiological and psychometric studies have provided evidence that some symptoms of venous disease might reflect a psychosomatic rather than organic disorder. Traditionally, plant extracts are prescribed to alleviate such symptoms. Since benzodiazepines (BZ) and BZ-like compounds are present in various plants, we studied potential interactions of ‘phlebotropic’ drugs with BZ receptors. Methods: Six drug preparations used in phlebology and extracts of hop and valerian were tested for neuronal and mitochondrial BZ receptor binding activity in vitro. In addition, plasma samples of volunteers who ingested phlebotropic drugs for 3 weeks were assayed for the presence of BZ-like activity. Results: All phlebotropic drug preparations interacted weakly with central and/or peripheral BZ receptors in vitro. Their diazepam-equivalent concentrations were, however, too low to be of pharmacological relevance. No binding activity was recovered in the blood of volunteers pretreated with phlebotropic drugs. Conclusion: The positive influence of so-called ‘phlebotropic’ drugs on the subjective symptoms of venous disease is not mediated through BZ receptors.

New Dimeric Tetrapeptide Enkephalin AnaloguesHydrophilic Spacer Length and Configuration Affects Potency and Receptor Selectivity

1994 ◽  
Vol 49 (3) ◽  
pp. 407-411
Author(s):  
Janusz Stępiński ◽  
S. William Tam
Keyword(s):  
Receptor Binding ◽  
Opioid Peptide ◽  
Binding Activity ◽  
High Potency ◽  
Spacer Length ◽  
Receptor Selectivity ◽  
Receptor Binding Activity ◽  
Peptide Analogues ◽  
Opioid Receptor Binding

AbstractThree new bivalent opioid peptide analogues, 1,3-di-(tyrosyl-D-alanyl-glycyl-phenylalanylamido)-2-propanol, 1,4-di-(tyrosyl-D-alanyl-glycyl-phenylalanylamido)-(2R, 3S)-butanediol and 1,4-di-(tyrosyl-D-alanyl-glycyl-phenylalanylamido)-(2R,3R)-butanediol, were synthesized and tested in vitro for μ, δ and ϰ receptor affinities. They were found to have potent opioid receptor binding activity. The (2S,3S)-butanediol bridge configuration yielded selectivity and high potency for μ and ϰ receptors, while the (2R,3R)-butanediol bridge configuration yielded high potency and selectivity for δ receptors. It thus appears that changes in the length and configuration of the polyhydroxyl bridge in dimeric enkephalin analogues can produce a shift in receptor selectivity profiles and therefore suggest the possibility of developing more selective drugs.

scholarly journals Chemical composition and biological effects of kratom (Mitragyna speciosa): In vitro studies with implications for efficacy and drug interactions

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
D. A. Todd ◽  
J. J. Kellogg ◽  
E. D. Wallace ◽  
M. Khin ◽  
L. Flores-Bocanegra ◽  
...  
Keyword(s):  
Opioid Receptor ◽  
Biological Effects ◽  
Binding Activity ◽  
Protein Signaling ◽  
Cytochrome P450 Enzymes ◽  
Mitragyna Speciosa ◽  
Receptor Binding Activity ◽  
Functional Profiles

Abstract The safety and efficacy of kratom (Mitragyna speciosa) for treatment of pain is highly controversial. Kratom produces more than 40 structurally related alkaloids, but most studies have focused on just two of these, mitragynine and 7-hydroxymitragynine. Here, we profiled 53 commercial kratom products using untargeted LC–MS metabolomics, revealing two distinct chemotypes that contain different levels of the alkaloid speciofoline. Both chemotypes were confirmed with DNA barcoding to be M. speciosa. To evaluate the biological relevance of variable speciofoline levels in kratom, we compared the opioid receptor binding activity of speciofoline, mitragynine, and 7-hydroxymitragynine. Mitragynine and 7-hydroxymitragynine function as partial agonists of the human µ-opioid receptor, while speciofoline does not exhibit measurable binding affinity at the µ-, δ- or ƙ-opioid receptors. Importantly, mitragynine and 7-hydroxymitragynine demonstrate functional selectivity for G-protein signaling, with no measurable recruitment of β-arrestin. Overall, the study demonstrates the unique binding and functional profiles of the kratom alkaloids, suggesting potential utility for managing pain, but further studies are needed to follow up on these in vitro findings. All three kratom alkaloids tested inhibited select cytochrome P450 enzymes, suggesting a potential risk for adverse interactions when kratom is co-consumed with drugs metabolized by these enzymes.

THE ASSAY OF HUMAN FOLLICLE-STIMULATING HORMONE PREPARATIONS: THE CHOICE OF A SUITABLE STANDARD

1979 ◽  
Vol 92 (4) ◽  
pp. 599-614 ◽  
Author(s):  
R. Marana ◽  
D. M. Robertson ◽  
H. Suginami ◽  
E. Diczfalusy
Keyword(s):  
Receptor Binding ◽  
Binding Assay ◽  
Binding Activity ◽  
Human Pituitary ◽  
Reactive Material ◽  
Receptor Binding Assay ◽  
Receptor Binding Activity ◽  
Suitable Standard ◽  
Urinary Fsh

ABSTRACT Eleven pituitary or urinary preparations of varying purity were assayed for FSH activity by an in vitro bioassay method, a receptor binding assay (RBA) technique and a radioimmunoassay (RIA) procedure, employing two anti-FSH sera with and without absorption with hCG. All methods were specific for hFSH, since other glycoproteins (hFSHα and hFSHβ subunits, hLH, hCG and hTSH) elicited little, if any, response. A partially purified hFSH preparation (1st IRP of Human Pituitary Gonadotrophins (FSH and LH/ICSH) for bioassay, code No. 69/104) was used as standard in all assays. In addition, potency estimates were expressed in terms of a highly purified hFSH preparation (hFSH-Kabi, Lot No. 19344) and in terms of the hMG (2nd IRP). Significant differences in the ratios of biological activity to receptor binding activity (B/R) and to immunological reactivity (B/I) were observed between preparations which were unrelated to their level of purity. The use of the 69/104 preparation as standard gave significantly higher B/R and B/I ratios than the use of the hMG (2nd IRP) and of a highly purified hFSH preparation. In addition, the use of the hMG (2nd IRP) as a standard gave significantly higher B/R ratios than that of the highly purified hFSH preparation. These results indicate that the 69/104 and hMG (2nd IRP) preparations contain significantly more biologically inactive receptor binding material than the more extensively purified hFSH preparation. Furthermore, the 69/104 preparation contains significantly more biologically inactive immunologically reactive material than both hMG reference standards and the highly purified hFSH preparation. It is concluded that, because of the presence in the 69/104 preparation of relatively large quantities of biologically inactive material which behaves in both the receptor binding assay (RBA) and radioimmunoassay (RIA) procedures as hFSH, this preparation is unsuitable as standard for the quantitation of FSH activity by methods other than bioassays. For the same reason, the relatively crude 2nd IRP (but not its replacement, the 1st IS for human urinary FSH and LH for bioassay) appears to be unsuitable as a standard for the assay of hFSH by RBA procedures. Among the limited number of preparations studied, a highly purified pituitary hFSH preparation appears to be the most satisfactory as a provisional standard for hFSH assays, although even this material contains some biologically inactive hFSH-like material.

Isolation and characterization of distinct bioactive forms of LH from male buffalo pituitaries: differences localized to their α subunits

1994 ◽  
Vol 143 (2) ◽  
pp. 313-323 ◽  
Author(s):  
M R Sairam ◽  
A A H Zaky ◽  
A A Hassan
Keyword(s):  
Receptor Binding ◽  
Binding Activity ◽  
Α Subunit ◽  
Basic Fraction ◽  
Isolation And Characterization ◽  
Receptor Binding Activity ◽  
Acidic Fraction ◽  
Α Subunits

Abstract The isolation of highly purified forms of pituitary LH from Egyptian male (Nile) buffaloes is described. The total LH content (receptor binding activity) which was approximately 30 to 50 fold higher than FSH in the pituitary could be divided into three pools based upon fractionation patterns on a cation exchanger. The acidic fraction which also contained FSH was not purified to homogeneity. A basic fraction (bu-LH-2; 300 mg/kg anterior pituitary) and a very basic fraction (bu-LH-3; 80 mg/kg) were both highly purified and free of FSH activity as tested by specific FSH receptor and immunoassays. The basic buffalo LH fraction, bu-LH-2, was as active as highly purified ovine LH (oLH). The most basic form of buffalo LH, bu-LH-3, was, however, about twice as active as highly purified oLH in the in vitro bioassay using mouse Leydig tumour (MA-10) cells. In a receptor binding assay employing 125I-labelled buffalo LH (bu-LH-3) and porcine testicular membranes, the affinity of bu-LH-3 was about five times higher than purified oLH. The Mr of both forms of purified buffalo LH and subunits was similar to that of oLH. Amino acid composition of buffalo LH was also very similar to oLH except for small differences. Fractionation by fast protein liquid chromatography on Mono-Q columns revealed further evidence of microheterogeneity in each of the pools of buffalo LH with bu-LH-3 exhibiting a predominant single component. By reverse-phase high-pressure liquid chromotography analysis we have localized differences in the two purified isoforms of male buffalo LH to the α subunit. It is suggested that differences in biological potencies could be due to variations in terminal glycosylation and/or differences in branching of this subunit which is known to be important for signal transduction. Journal of Endocrinology (1994) 143, 313–323

scholarly journals The (ProB27, ThrB28) human insulin analogue is more potent and more rapidly absorbed from subcutis than human insulin

2002 ◽  
pp. 227-233 ◽  
Author(s):  
R Clausen ◽  
TG Jorgensen ◽  
KH Jorgensen ◽  
AH Johnsen ◽  
JJ Led ◽  
...  
Keyword(s):  
Blood Glucose ◽  
Insulin Receptor ◽  
Human Insulin ◽  
Binding Activity ◽  
Glucose Lowering ◽  
Recombinant Receptors ◽  
Receptor Binding Activity ◽  
Human Insulin Receptor ◽  
Igf Receptors

OBJECTIVE: To test the physiological properties of human insulin in which the amino acids Thr (B27) and Pro (B28) are interchanged (PT insulin). This was hypothesised to prevent dimerisation and accelerate the absorption from s.c. tissue without altering the affinity for the insulin receptor. DESIGN: PT insulin was expressed in Pichia pastoris and processed in vitro. The purified compound was used for physiological investigations. METHODS: Receptor binding activity to insulin and IGF receptors was evaluated in a competition assay using iodinated PT insulin and recombinant receptors while growth induction properties were evaluated by thymidine incorporation. Absorption kinetics from pig subcutis was investigated by measuring the disappearance of iodinated PT insulin. The potency was evaluated by measuring the blood glucose lowering activity in mice. RESULTS: The absorption of PT insulin was accelerated compared with human insulin, although still slower than Asp (B28) insulin. Human and PT insulin had similar affinities for the human insulin receptor (K(d)=3.6 x 10(-12) vs 5.2 x 10(-12) mol/l) while the affinity for the IGF receptor was four times higher for PT insulin than for human insulin (K(d)=3.4 x 10(-8) vs 1.3 x 10(-7) mol/l). This resulted in a slightly higher DNA synthesis when assayed in intermediary insulin concentrations. The blood glucose lowering effect in mice exceeded the effect of human insulin (integral 0-60 min: 61.4+/-7 vs 30+/-4, n=6, P=0.046). CONCLUSIONS: PT insulin is absorbed faster and is more potent than human insulin. Although PT insulin stimulates growth more than human insulin, this will not prevent its use in the clinic, but the main interest will probably focus on investigations to clarify the paradox of full biological activity in connection with the recently described lack of structure in the B-chain.

Characterization of a novel peripheral pro-lipolytic mechanism in mice: role of VGF-derived peptide TLQP-21

2011 ◽  
Vol 441 (1) ◽  
pp. 511-522 ◽  
Author(s):  
Roberta Possenti ◽  
Giampiero Muccioli ◽  
Pamela Petrocchi ◽  
Cheryl Cero ◽  
Aderville Cabassi ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Ex Vivo ◽  
Binding Capacity ◽  
Binding Activity ◽  
Metabolic Complications ◽  
Novel Approach ◽  
Receptor Binding Activity ◽  
Treatment Of Obesity

The peptides encoded by the VGF gene are gaining biomedical interest and are increasingly being scrutinized as biomarkers for human disease. An endocrine/neuromodulatory role for VGF peptides has been suggested but never demonstrated. Furthermore, no study has demonstrated so far the existence of a receptor-mediated mechanism for any VGF peptide. In the present study, we provide a comprehensive in vitro, ex vivo and in vivo identification of a novel pro-lipolytic pathway mediated by the TLQP-21 peptide. We show for the first time that VGF-immunoreactivity is present within sympathetic fibres in the WAT (white adipose tissue) but not in the adipocytes. Furthermore, we identified a saturable receptor-binding activity for the TLQP-21 peptide. The maximum binding capacity for TLQP-21 was higher in the WAT as compared with other tissues, and selectively up-regulated in the adipose tissue of obese mice. TLQP-21 increases lipolysis in murine adipocytes via a mechanism encompassing the activation of noradrenaline/β-adrenergic receptors pathways and dose-dependently decreases adipocytes diameters in two models of obesity. In conclusion, we demonstrated a novel and previously uncharacterized peripheral lipolytic pathway encompassing the VGF peptide TLQP-21. Targeting the sympathetic nerve–adipocytes interaction might prove to be a novel approach for the treatment of obesity-associated metabolic complications.

Sign in / Sign up

Export Citation Format

Share Document