The interactions of phencyclidine (PCP) and related agonists with putative receptor blockers were studied on cerebellar Purkinje neurons using electrophysiological techniques. Depressions induced by PCP or dexoxadrol, a sigma receptor agonist, were markedly antagonized by the PCP receptor antagonist metaphit, which acylates PCP receptors via its isothiocyanate moiety. Conversely, the depressant effect of levoxadrol, the (-) isomer of dexoxadrol, was not affected by metaphit. Further evidence that metaphit's specific antagonism of dexoxadrol- and PCP-mediated depressions was derived from data showing that drugs which respectively acylate mu and delta opioid receptors, benzimidazole isothiocyanate and fentanyl isothiocyanate, do not antagonize the actions of either PCP or dexoxadrol. Moreover, tyramine, which like PCP acts as an indirect norepinephrine agonist, is not antagonized by metaphit. These observations support the concept that metaphit causes a pharmacologically specific and irreversible antagonism of the effects of both PCP and dexoxadrol in the cerebellum. ...
... Phencyclidine (PCP)-induced catalepsy in pigeons, which is a pharmacologically specific and stereoselective phenomenon, was used to study pharmacological consequences of the proposed covalent bonding of metaphit to PCP sites. Metaphit pretreatment increased the cataleptic effects induced by cumulative doses of PCP-type drugs (ie, PCP, ketamine and m-amino PCP) and of drugs that have PCP-like actions (i.e., dexoxadrol, LY 154716 and cyclazocine)...
The binding of [3H]phencyclidine (PCP) to receptors in rat brain cortex has been studied. Two receptors have been detected, a high affinity receptor site with a KD of 23.5 +/- 7.4 nM and a low affinity site with a KD of 7.6 +/- 1.8 microM. The binding of [3H]PCP to its receptors was pH and temperature dependent and was destroyed by heat-denaturation. The binding of [3H]PCP was inhibited by compounds which produce PCP-like behavioral effects including dexoxadrol, etoxadrol and ketamine as well as a novel series of benz(f)isoquinolines. The low affinity site was blocked by PCP, etoxadrol and (+)-SKF-10,047 but not morphine or leu-enkephalin, suggesting that it also represents a specific PCP site. Stereoselective displacement of PCP at the high affinity receptor was observed with the isomers of cyclazocine, cyclorphan, SKF-10,047 and dioxadrol (dexoxadrol and levoxadrol). Naloxone, 4,5,6,7-tetrahydroisoxazolo(S,4-C)pyridin-3-ol (THIP) hydrate and haloperidol inhibited binding poorly (Ki greater than 1 microM), suggesting that these compounds do not interact significantly with the high affinity PCP receptor in vivo. The affinity of ligands for the phencyclidine receptor was highly correlated (r = 0.714, P less than 0.01) with their potency to produce catalepsy in pigeons.
/SRP:/ Immediate first aid: Ensure that adequate decontamination has been carried out. If patient is not breathing, start artificial respiration, preferably with a demand valve resuscitator, bag-valve-mask device, or pocket mask, as trained. Perform CPR if necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on the left side (head-down position, if possible) to maintain an open airway and prevent aspiration. Keep patient quiet and maintain normal body temperature. Obtain medical attention. /Poisons A and B/
/SRP:/ Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with 0.9% saline (NS) during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 mL/kg up to 200 mL of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poisons A and B/
(3)H-Dexoxadrol, a dissociative anesthetic, binds with high affinity to specific sites in rat brain (membrane binding and light microscopic autoradiography). Various phencyclidine analogues compete for (3)H-dexoxadrol sites in a slightly different manner than against (3)H-phencyclidine binding sites. As for (3)H-phencyclidine binding, (3)H-dexoxadrol binding sites are highly concentrated in brain regions such as the cortex and the hippocampus. However, other areas such as the hypothalamus are enriched only in (3)H-dexoxadrol binding sites. This suggests that (3)H-dexoxadrol binds to phencyclidine-related sites in certain brain regions but not in others. In the human forebrain, (3)H-dexoxadrol binding sites are distributed as in the rat brain and mainly found in the caudate, putamen and cortex.
[EN] PEPTIDE-BASED MULTIPLE-DRUG DELIVERY VEHICLE<br/>[FR] VÉHICULE D'ADMINISTRATION DE MÉDICAMENTS MULTIPLES À BASE DE PEPTIDES
申请人：ARIEL-UNIVERSITY RES AND DEV COMPANY LTD
公开号：WO2017068577A1
公开（公告）日：2017-04-27
A molecular structure comprising a targeting moiety, a multi-functional peptide platform and a plurality of controllably released bioactive agents attached thereto is provided herein.
本文提供了一种包括靶向基团、多功能肽平台和附着在其上的多种可控释放的生物活性剂的分子结构。
[EN] COMPOUNDS (CYSTEIN BASED LIPOPEPTIDES) AND COMPOSITIONS AS TLR2 AGONISTS USED FOR TREATING INFECTIONS, INFLAMMATIONS, RESPIRATORY DISEASES ETC.<br/>[FR] COMPOSÉS (LIPOPEPTIDES À BASE DE CYSTÉINE) ET COMPOSITIONS EN TANT QU'AGONISTES DES TLR2 UTILISÉS POUR TRAITER DES INFECTIONS, INFLAMMATIONS, MALADIES RESPIRATOIRES ENTRE AUTRES
申请人：IRM LLC
公开号：WO2011119759A1
公开（公告）日：2011-09-29
The invention provides a novel class of compounds viz. generally lipopeptides like Pam3CSK4, immunogenic compositions and pharmaceutical compositions comprising such compounds and methods of using such compounds to treat or prevent diseases or disorders associated with Toll-Like Receptors 2. In one aspect, the compounds are useful as adjuvants for enhancing the effectiveness a vaccine.
[EN] PRODRUGS OF SECONDARY AMINE COMPOUNDS<br/>[FR] PROMÉDICAMENTS DE COMPOSÉS AMINE SECONDAIRES
申请人：ALKERMES PHARMA IRELAND LTD
公开号：WO2013088255A1
公开（公告）日：2013-06-20
The present invention relates to compounds of Formula (I).
本发明涉及式(I)的化合物。
PYRIDINE AND PIPERIDINE DERIVATIVES AND USE THEREOF
申请人：Purdue Pharma L.P.
公开号：US20150141434A1
公开（公告）日：2015-05-21
The invention provides compounds that are useful as sodium channel blockers. In one aspect, the invention provides compounds of Formula I:
or pharmaceutically acceptable salts, solvates, hydrates, or diastereomers thereof, wherein R
1
, R
4
, X, G, n, p, W
1
, W
2
, W
3
, W
4
, and the E ring are defined in the disclosure. In certain embodiments, the invention provides compounds of Formulae II-XIII as set forth supra. The invention also provides the use of compounds of any of the above discussed formulae to treat a disorder responsive to blockade of sodium channels. In one embodiment, Compounds of the Invention are useful for treating pain.
[EN] CANNABINOID RECEPTOR MODULATORS<br/>[FR] MODULATEURS DES RÉCEPTEURS DES CANNABINOÏDES
申请人：ARENA PHARM INC
公开号：WO2012116279A1
公开（公告）日：2012-08-30
Provided are certain methods useful in the treatment of pain comprising administering a compound of Formula Ia and pharmaceutical compositions thereof that modulate the activity of the cannabinoid CB2 receptor.
