ABSTRACT
A cyclic analog of enkephalin, cyclo(Lys-Tyr-DMet-Gly-Phe-Pro-) and two corresponding linear hexapeptides with lysine residue on the N- and C-termini of the pentapeptide sequence, Lys-Tyr-DMet-Gly-Phe-Pro and Tyr-DMet-Gly-Phe-Pro-Lys were synthesized by classical and solid phase methods of peptide chemistry. The cyclic analog exhibited significantly prolonged analgesic effect, evaluated by the "tail pinch" method after intracysternal injection to mice. The cycloanalog also had a weak influence on the peripheral opiate receptors of the isolated segment of guinea pig iliac intestine. Addition of the lysine residue to the N-terminus of the pentapeptide sequence enhanced by an order of magnitude the selectivity of binding of the analog with opiate receptors of mu-type.
Subject(s)
Analgesics/chemical synthesis , Enkephalins/chemical synthesis , Peptides, Cyclic/chemical synthesis , Amino Acid Sequence , Analgesics/pharmacology , Animals , Circular Dichroism , Delayed-Action Preparations , Enkephalins/pharmacology , Guinea Pigs , Ileum/drug effects , Ileum/metabolism , In Vitro Techniques , Mice , Molecular Sequence Data , Peptides, Cyclic/pharmacology , Receptors, Opioid/drug effectsABSTRACT
Biological properties of a novel vasopressin analogue were investigated. It was found that this analogue has no vasopressor and oxytocic activities but it exhibits a selective antidiuretic effect which is weaker than that of adiuretin (DDAVP). Novel analogue inhibits vasopressor, oxytocic and antidiuretic effects caused by arginine--vasopressin. The usefulness of novel compound as a pharmacological tool--vasopressin antagonist is suggested.
Subject(s)
Arginine Vasopressin/analogs & derivatives , Arginine Vasopressin/antagonists & inhibitors , Diuretics/antagonists & inhibitors , Animals , Arginine Vasopressin/administration & dosage , Arginine Vasopressin/pharmacology , Deamino Arginine Vasopressin/pharmacology , Female , Male , Rats , Time FactorsABSTRACT
In the experiments on mice there were analysed the effects of arginine-vasopressin (AVP) and its analogue des-glycine-arginine-vasopressin (DG-AVP) on the extinction of the conditioned reaction of passive avoidance and the reproduction of memory trace in amnesia caused by detaining the animal in the dangerous section of the unit after electrocutaneous stimulation. An increase of resistance of the conditioned reaction to a sharp extinction at systemic administration of AVP and DG-AVP was shown.
Subject(s)
Amnesia/drug therapy , Arginine Vasopressin/analogs & derivatives , Arginine Vasopressin/pharmacology , Conditioning, Classical/drug effects , Extinction, Psychological/drug effects , Amnesia/etiology , Animals , Arginine Vasopressin/therapeutic use , Avoidance Learning/drug effects , Drug Evaluation, Preclinical , Electric Stimulation , Male , Memory/drug effects , Mice , Mice, Inbred BALB CABSTRACT
Tritiated vasopressin analogue, [8-L-arginine, 9-desglycineamide]-vasopressin was prepared from its diiodo-derivative by means of catalytic reductive dehalogenation. The reaction products were purified by reversed-phase HPLC resulting in a labelled peptide with high specific radioactivity (629 TBq/mmol).
Subject(s)
Arginine Vasopressin/analogs & derivatives , Arginine Vasopressin/chemical synthesis , Chromatography, High Pressure Liquid , In Vitro Techniques , TritiumSubject(s)
Brain/physiology , Electroencephalography , Neuropeptides/physiology , Animals , Electrodes , Female , Male , RabbitsABSTRACT
Three new analogues of vasopressin, viz. des-Gly9-[Phe2, Orn8]vasopressin, diglycyl-des-Gly9-[Phe2, Orn8]vasopressin, and diglycyl-des-Gly9-[Val4, Orn8]vasopressin, were synthesized to investigate the structure-function relationship. Hormonal (vasopressor, antidiuretic, uterotonic, galactogogic) activities of the new compounds were determined, their effect on elaboration and retention of the active avoidance behaviour in rats was studied.
Subject(s)
Vasopressins/chemical synthesis , Animals , Avoidance Learning/drug effects , Chemical Phenomena , Chemistry , Circular Dichroism , Conditioning, Classical/drug effects , Memory/drug effects , Ornipressin/analogs & derivatives , Ornipressin/chemical synthesis , Ornipressin/pharmacology , Rabbits , Rats , Vasopressins/pharmacologySubject(s)
Stress, Psychological/drug therapy , Vasopressins/therapeutic use , Adaptation, Physiological/drug effects , Animals , Brain/drug effects , Brain/physiopathology , Dose-Response Relationship, Drug , Drug Evaluation, Preclinical , Male , Rats , Stress, Psychological/blood , Stress, Psychological/physiopathologyABSTRACT
2D 1H-NMR spectra of des-Gly9-[Arg8]vasopressin in dimethylsulfoxide have been taken and the 1H resonances have been assigned. The coupling constants and amide proton temperature coefficients (delta delta/delta T) have been measured and the NOE cross-peaks in the NOESY spectrum have been analyzed. The most essential information on the spatial structure of des-Gly9-[Arg8]vasopressin is extracted from the low delta delta/delta T value for Asn5 amide proton and from the NOE between the Cys1 and Cys6 alpha-protons. A diminished accessibility of the Asn5 NH proton for the solvent is ascribed to the presence of a beta-turn in the fragment 2-5. The distance between the Cys1 and Cys6 C alpha H protons seems to be less than 4 A. These constraints were taken into account in the conformational analysis of the title peptide. The derived set of the low-energy backbone conformations was analyzed against the background of the all available NMR data. The most probable conformation of the cyclic moiety in des-Gly9-[Arg8]vasopressin was found to be the type III beta-turn. The corner positions are occupied by the residues 3, 4, while the residues 1-2 and 5-6 are at the extended sites. Some NMR data indicate that this structure is in a dynamic equilibrium with other minor conformers.
Subject(s)
Arginine Vasopressin/analogs & derivatives , Amino Acid Sequence , Magnetic Resonance Spectroscopy , Models, Molecular , Protein ConformationSubject(s)
Avoidance Learning/drug effects , Extinction, Psychological/drug effects , Vasopressins/pharmacology , 5-Hydroxytryptophan/pharmacology , Animals , Arginine Vasopressin/analogs & derivatives , Arginine Vasopressin/pharmacology , Conditioning, Classical/drug effects , Female , Lypressin/analogs & derivatives , Lypressin/pharmacology , Male , Rats , Terlipressin , Time FactorsABSTRACT
Perfusion of the snail (Helix lucorum L.) CNS with DG-AVP (concentration 10(-6) M) in the course of low frequency intracellular stimulation (2-4-minute interval) of the defensive reflex command neurons led to an increase in the excitability. It was expressed both in the reduction of the spike generation latency, in the increased number of spikes in response to fixed stimuli, and in the activation of pacemaker potentials. If DG-AVP was added to the medium during endoneuronal habituation, there was no increase in the excitability. It is supposed that modification of the neuronal excitability may be caused by the DG-AVP effect on the pacemaker mechanism.
Subject(s)
Arginine Vasopressin/analogs & derivatives , Escape Reaction/drug effects , Helix, Snails/drug effects , Neurons/drug effects , Reflex/drug effects , Action Potentials/drug effects , Animals , Arginine Vasopressin/pharmacology , Electric Stimulation , In Vitro Techniques , Reaction Time/drug effectsABSTRACT
The effects of synthetic neuropeptide LH-RH and its analogues were studied in experiments on 174 white male rats. The influence of the substances was shown on instrumental avoidance learning in Y-shaped maze. Convulsive and anticonvulsive effects of the preparations were studied on experimental model of corasol seizures. The analgetic effect of the substances was evaluated by behavioural pain reaction to electrical stimulation of the tail root. Analgetic, anticonvulsive, and psychostimulating LH-RH properties confirm polyfunctionality and "pleiotropy" of neuropeptides as a class of new endogenous informational compounds.
Subject(s)
Analgesics , Anticonvulsants , Central Nervous System Stimulants , Gonadotropin-Releasing Hormone/pharmacology , Animals , Avoidance Learning/drug effects , Conditioning, Operant/drug effects , Gonadotropin-Releasing Hormone/analogs & derivatives , Male , Memory/drug effects , Pentylenetetrazole/antagonists & inhibitors , RatsABSTRACT
Forty-seven males suffering from paranoid schizophrenia running a paroxysm-like progressive course were treated with the synthetic neuropeptide arginine-vasopressin, a hormone of the posterior lobe of the hypophysis. The therapeutic effect of the hormone was confirmed by a complex of clinical, laboratory and pathopsychological techniques. Both objective methods of investigation and subjective assessment of the patients demonstrated a high efficacy of the drug which was expressed in a marked psychoenergizing action, a beneficial effect on emotional disorders, a memory improvement and a favourable influence on the apatho-abulic manifestations.
Subject(s)
Antipsychotic Agents , Arginine Vasopressin/therapeutic use , Schizophrenia, Paranoid/drug therapy , Adult , Follow-Up Studies , Humans , Male , Middle Aged , SyndromeABSTRACT
The effect of vasopressin on learning, habituation and habit recovery in rat before and after electrolytic ablation of locus coeruleus, nuclei dorsalis et medialis raphe and pars compacta substantiae nigrae was studied by behavioural methods. The rats were learned with positive reinforcement in a T-shaped maze and with negative reinforcement in a U-shaped maze. It was found that improvement of trace consolidation and acceleration of learning were in many cases dependent on the activity level of the dophaminergic, noradrenergic and to a lesser degree on that of serotoninergic brain systems.
