Ifenprodil Tartrate Research Articles

Very mild improvement of adolescent PTSD found with ifenprodil tartrate

The Brown University Child & Adolescent Psychopharmacology UpdateVolume 24, Issue 5 p. 6-6 Research briefs Very mild improvement of adolescent PTSD found with ifenprodil tartrate Alison Knopf, Alison KnopfSearch for more papers by this author Alison Knopf, Alison KnopfSearch for more papers by this author First published: 12 April 2022 https://doi.org/10.1002/cpu.30670Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article. Volume24, Issue5May 2022Pages 6-6 RelatedInformation

Ifenprodil tartrate treatment of adolescents with post-traumatic stress disorder: A double-blind, placebo-controlled trial

BackgroundSeveral lines of evidence suggest that glutamatergic neurotransmission via the N-methyl-D-aspartate (NMDA) receptor plays a role in certain behavioral manifestations common to Post-Traumatic Stress Disorder (PTSD). Ifenprodil tartrate is a neuroprotective agent that binds to the GluN2B subunit of the NMDA receptor. The aim of this study is to confirm whether ifenprodil tartrate is effective in the adolescent PTSD patients. MethodsThis is a randomized, double-blind, placebo‐controlled trial. Ten adolescent (13 to 18 years old) PTSD patients were randomized into two arms: placebo (n = 4), 40 mg/day ifenprodil tartrate (n = 6) for 4 weeks. All of the patients were assessed by IES-R-J (Primary outcome measure), TSCC-J, CDRS-R, DSRS-C-J and CGI-I. ResultsA comparison of baseline IES-R-J total scores and 4-week end-point scores showed a mild trend of improvement (p = 0.0895) and the difference score was -9.314. A comparison of baseline scores and 2-week intermediate-point scores showed that IES-R-J hyperarousal subscores and TSCC-J subscores (dissociation subscores, sexual concerns subscores) improved significantly. A comparison of baseline TSCC-J sexual concerns subscores and 4-week end-point scores improved significantly. ConclusionsOur study may prove to be an short-term effective alternative safe treatment for adolescent patients with PTSD.

Study of effects of ifenprodil in patients with methamphetamine dependence: Protocol for an exploratory, randomized, double-blind, placebo-controlled trial.

AimsPharmacotherapy for methamphetamine dependence has not yet been developed in Japan or elsewhere in the world. Ifenprodil is a blocker of G protein‐activated inwardly rectifying potassium channels that play a key role in the mechanism of action of addictive substances. Our aim is to examine the safety, efficacy, and outcomes of ifenprodil for the treatment of methamphetamine dependence in a randomized, double‐blind, placebo‐controlled trial.MethodsThe recruitment of outpatients with methamphetamine dependence began in January 2018. The patients will be randomized into three arms: placebo, 60 mg/d ifenprodil, or 120 mg/d ifenprodil. Placebo or ifenprodil will be taken for 84 days. We will use Cerocral fine granule 4%® (ifenprodil tartrate). Follow‐up assessments will be conducted for 84 d after the drug administration period. All of the patients will be assessed by self‐administered questionnaires and urine tests. The primary outcome will be the presence or absence of methamphetamine use during the 84‐day administration period in the 120 mg/d ifenprodil and placebo groups. Secondary outcomes will include the number of days and percentage of days of abstinence from methamphetamine use, positive urine for methamphetamine, relapse risk, and drug craving.DiscussionThis study is the first clinical trial of ifenprodil treatment for methamphetamine dependence and is designed as an intervention test with off‐label drug use. The present study is expected to provide evidence of the effects of ifenprodil treatment on methamphetamine dependence.Trial registryThis trial was registered in the UMIN clinical trial registry (UMIN000030849; date of registration: January 17, 2018).

思春期の心的外傷後ストレス障害（PTSD）患者を対象にしたイフェンプロジル酒石酸塩の有効性を検討するためのプラセボ対照二重盲検比較試験

思春期の心的外傷後ストレス障害（PTSD）患者を対象にしたイフェンプロジル酒石酸塩の有効性を検討するためのプラセボ対照二重盲検比較試験

Anti-proliferative activity of haloperidol in B16 mouse and human SK-MEL-28 melanoma cell lines

Sigma receptors are present in cancer cell lines. The aim of the present study is to evaluate the anti-tumor activity of a series of sigma 1, sigma 2 and sigma 1/2 ligands in B16 melanoma cell lines. Proliferation, apoptosis, intracellular ATP content, cell cycle and molecular regulators were analyzed. Cell growth was determined using the sulforhodamine B (SRB) colorimetric cytotoxicity assay. Apoptosis was assessed by flow cytometry and DNA fragmentation, using ELISA cell death assay. ATP content was measured spectrofluorometrically and cell cycle analysis was performed by flow cytometry. The cytoplasmic and nuclear expression of cell cycle regulatory molecules, cyclin D and CDK2 (cyclin dependent kinase 2) were determined by Western blot analysis and quantified by densitometry. The sigma ligands in single digit micromolar concentrations inhibited B16 and multidrug-resistant B16 COL/R cell growth, leading to cell death at higher concentrations. The potency order was: haloperidol, reduced-haloperidol, ifenprodil tartrate, opipramol and carbetapentane citrate. B16 COL/R cells were to some extent, less sensitive to sigma ligands. Further studies have shown that the growth inhibitory effect of sigma ligands could be attributed to G1 arrest of the cell cycle, mediated by a marked decrease in cytoplasmic and nuclear cyclin D and CDK2 protein expression, though haloperidol induced loss of cell viability due to apoptosis. Sigma ligands induced an early decrease in ATP content. These data stimulated us to examine the combined anti-proliferative activity of haloperidol and the tyrosine kinase inhibitor imatinib mesylate (STI 571), on SK-MEL-28 human melanoma cells. Preliminary experiments demonstrated a marked synergistic interaction between the two agents.

Behavioral effects of NMDA receptor agonists and antagonists in combination with nitric oxide-related compounds

Responding of rats was maintained under a 120-response fixed ratio (FR) schedule of food delivery, and animals received individual and combined injections of N-methyl- d-aspartic acid (NMDA), phencyclidine hydrochloride, (+)-MK-801 hydrogen maleate (MK-801), (±)-2-amino-5-phosphonopentanoic acid (AP5), 7-chlorokynurenic acid (7CK), ifenprodil tartrate, N G-nitro- l-arginine methyl ester hydorchloride ( l-NAME), 7-nitroindazole, aminoguanidine hemisulfate, l-arginine, molsidomine, sodium nitroprusside, and 8-(diethylamino)octyl 3,4,5-trimethoxybenzoate hydrochloride (TMB-8). Behavioral suppression after NMDA was completely and dose-dependently reversed by MK-801, phencyclidine, AP5, and aminoguanidine; partially and dose-dependently attenuated by molsidomine, ifenprodil, and 7CK; and not attenuated at all by l-NAME, 7-nitroindazole, or TMB-8. These findings suggested that behavioral suppression after NMDA was associated with nitric oxide from the inducible synthase. In a second series of experiments, comparable behavioral suppression by 0.1 mg/kg MK-801, but not 3 mg/kg phencyclidine, was attenuated by nitroprusside, molsidomine, and l-arginine, suggesting that suppressions from MK-801 and phencyclidine were mediated by different final common pathways, and that behavioral suppression from MK-801, but not phencyclidine, may be associated with Ca 2+-dependent nitric oxide.

Effect of ifenprodil on ocular tissue circulation in rabbits.

Ifenprodil tartrate has long been employed as a cerebral vasodilator with alpha and N-methyl-D-aspartate (NMDA) receptor antagonistic activities. The purpose of this study was to evaluate the effects of ifenprodil on ocular circulation in rabbits. Experiments were performed during the dark phase in Dutch rabbits conditioned to a schedule of alternating 12-hr periods of light and dark. Effects on ocular tissue blood velocity were estimated using the laser speckle method in the iris, posterior choroid, and optic nerve head (ONH). Measurements of tissue blood velocity were performed both after intravenous injection of ifenprodil at a dose of 0.2 mg/kg, 0.1 mg/kg, and the same volume of the vehicle, and after topical instillation of 0.5% ifenprodil (50 microl) twice daily for 1, 3 and 20 days unilaterally in a masked manner. Intraocular pressure (IOP) was also measured during the experimental period. Intravenous administration of ifenprodil caused a significant increase in blood velocity in the ONH, choroid, and iris, but ONH circulation was affected at a lower dose than uveal circulation. In the topical instillation experiment, IOP in the ifenprodil-treated eye was significantly lower, by approximately 2 mmHg, than that in the contralateral eye when the laser speckle measurement was performed. Twice-daily, unilateral 0.5% ifenprodil instillation significantly increased blood velocity in the iris after 3 days and that in the ONH and posterior choroid after 20 days in the treated eye. Topical 0.5% ifenprodil increased blood velocity in the iris, posterior choroid, and ONH after multiple dosings. After systemic administration, ONH circulation appeared to be influenced at a lower dose than was uveal circulation.

Non-N-methyl-D-aspartate (NMDA) receptor antagonist 1,2,3, 4-tetrahydro-6-nitro-2,3-dioxo-benzo(f)quinoxaline-7-sulphonamide (NBQX) decreases functional disorders in cytotoxic brain oedema.

N-methyl-D-aspartate (NMDA) and non-NMDA receptors were found to be involved in development of functional disorders caused by hexachlorophene. In order to specify the role of glutamate receptors we studied the protective effects of the selective antagonist of the kainate/(+/-)-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor/channel 1,2,3,4-tetrahydro-6-nitro-2, 3-dioxo-benzo[f]quinoxaline-7-sulphonamide disodium (NBQX) and of the non-competitive NMDA receptor antagonist ifenprodil tartrate on coordinative motor behaviour of adult male Wistar rats as assessed in a simple 'ladder-test'. Neurotoxic injury of the cerebrum after hexachlorophene administration and putative amelioration after treatment with test substances was demonstrated histologically. Hexachlorophene-induced motor disturbance remitted spontaneously when stopping the noxis, but remittance occurred significantly earlier when NBQX [0.45 and 0.6 mg/kg intraperitoneal (i.p.)] was applied as well. Ifenprodil (0.15 to 1.2 mg/kg) did not improve the motor function. Vacuolation of white matter of the whole cerebrum was observed after 3 weeks of treatment with hexachlorophene. These morphological alterations caused by hexachlorophene treatment [central nervous system (CNS) vacuolation] spontaneously revert only after 5-6 weeks. The 5-day duration with test substances was too short for remission of vacuolation which thus may not apply to the situation after treatment with glutamate antagonists, despite improvement of motor function. The results suggest that kainate/AMPA receptor channels are at least partially involved in the mechanism of brain damage induced by hexachlorophene, however, the polyamine binding site of the NMDA receptor evidently is not involved.

粒子計測型血小板凝集計とずり応力惹起血小板凝集計による酒石酸イフェンプロジルの血小板凝集抑制作用の検討

粒子計測型血小板凝集計とずり応力惹起血小板凝集計による酒石酸イフェンプロジルの血小板凝集抑制作用の検討

Evaluation of Ifenprodil Efficacy on Exercise-Induced Tissue Ischemia in Stage II Arteriopathy by Measurement of Transcutaneous Oxygen Tension During a Standard Treadmill Test: Double-Blind Study of Injectable Ifenprodil Versus Placebo

Measurement of transcutaneous oxygen tension (TcPO2) is a noninvasive and easily reproducible method for objectifying and quantifying exercise ischemia in patients with stage II occlusive arterial disease. This technique is also used at rest to evaluate the therapeutic effect of vasoactive treatments. To objectively assess the effectiveness of a vasoactive treatment on the conditions of tissue perfusion, a randomized double-blind study of ifenprodil tartrate versus placebo was performed in 20 patients, whose TcPO2 was continuously measured while they walked on a treadmill. Patients treated with ifenprodil improved significantly as compared with the placebo group, for both the half-hypoxia area, representing the overall evolution of the tissue ischemia (+34.9% and -16.0%, respectively, p = 0.01), and the half-hypoxia recovery time, estimating the postexercise recovery time (+30.2% and -3.6%, respectively, p < 0.05). This study confirms that the continuous measurement of TcPO2 during the recovery phase after exercise represents an objective method for the evaluation and follow-up of patients with stage II intermittent claudication. The results enabled the objective assessment of ifenprodil efficacy on the evolution of tissue hypoxia.

P-404 - Antagonistic effects of ifenprodil tartrate on mild stress-induced hyperactivity in a novel design involving spontaneous hypertensive rats

P-404 - Antagonistic effects of ifenprodil tartrate on mild stress-induced hyperactivity in a novel design involving spontaneous hypertensive rats

The mode for the manifestation of the inhibitory effects of ifenprodil tartrate on platelet aggregation in vivo and ex vivo

The mode for the manifestation of the inhibitory effect of ifenprodil tartrate on platelet aggregation in vivo and ex vivo was studied in mice and men, respectively. The ifenprodil level in plasma reached the maximum in 20 min after oral administration of 30 mg ifenprodil tartrate/kg in mice, and it decreased over a 3 hr period after the administration. On the other hand, the maximal inhibitory effect was observed 60 min after the administration. Thus ifenprodil tartrate manifested its inhibitory effect on platelet aggregation only after the maximum plasma concentration of ifenprodil was reached. The same phenomenon was observed with the inhibitory effects of ifenprodil tartrate on platelet aggregation ex vivo in man. To clarify the reason for the delay in the manifestation of the inhibitory effects of ifenprodil, the ifenprodil contents in mouse platelets after the oral administration of the drug was measured. The pattern of change in the ifenprodil contents in platelets was found to resemble closely the pattern of the change in its inhibitory effects, suggesting that the manifestation of the inhibitory effects on platelet aggregation by oral administration of ifenprodil tartrate was directly related to the ifenprodil contents in platelets rather than the ifenprodil level in plasma.

O-149 - Combined effects of ifenprodil tartrate and calciua hopantenate on e-adrenoceptors in isolated canine saphenous veins

O-149 - Combined effects of ifenprodil tartrate and calciua hopantenate on e-adrenoceptors in isolated canine saphenous veins

Effects of ifenprodil glucuronide derivative on platelet aggregation and vasocontraction.

It has been supposed that ifenprodil glucuronide derivative, detectable in large amount in rabbit plasma, is related to the pharmacological actions by ifenprodil tartrate. However, a synthesized ifenprodil glucuronide derivative was found to have no effect on platelet aggregation and vasocontraction in vitro. These results indicate that ifenprodil itself rather than its glucuronide derivative manifested the pharmacological actions.

O-45 - Combined effects of ifenprodil tartrate and cardiovascular drugs on canine arteries

O-45 - Combined effects of ifenprodil tartrate and cardiovascular drugs on canine arteries

O-185 - Effect of ifenprodil tartrate on Ca2+ movement in canine arteries

O-185 - Effect of ifenprodil tartrate on Ca2+ movement in canine arteries

Inhibitory mechanism of ifenprodil tartrate on rabbit platelet aggregation

The effects of dl-erythro-4-benzyl-alpha-(4-hydroxyphenyl)-beta-methyl-l-piperidine-eth anol tartrate (ifenprodil tartrate) on rabbit platelet aggregation in vitro and ex vivo were studied. Ifenprodil tartrate inhibited platelet aggregation in vitro induced by ADP, collagen and epinephrine. It also inhibited 5-hydroxytryptamine (5-HT) uptake into platelets and 5-HT release from platelets. Since these inhibitory effects of ifenprodil tartrate on the functions of rabbit platelets were similar to the effects of imipramine, the effects of ifenprodil tartrate may be due to the stabilizing action of ifenprodil tartrate on the platelet membrane. The platelet aggregation by ADP was significantly inhibited in rabbits after oral administration of ifenprodil tartrate, the maximal plasma level of ifenprodil being reached at 20 ng/ml ex vivo, while the maximal level was only 1/40 of the minimal concentration of ifenprodil tartrate necessary to inhibit platelet aggregation in vitro. These results indicate that factors other than ifenprodil tartrate acting directly on the platelets (e.g., PGI2 which is an endogenous inhibitor of platelet aggregation) are involved in inducing the inhibitory effects of ifenprodil tartrate on platelet aggregation ex vivo. The effects of ifenprodil tartrate on both PGI2 release from the aorta and the inhibitory effects of PGI2 on platelet aggregation in vitro were investigated: PGI2 was found to intensify the inhibitory effects of ifenprodil tartrate on platelet aggregation in vitro, but there was little effect, if any, on PGI2 release. Therefore, it is considered that the ex vivo effects of ifenprodil tartrate might be due to its interaction with endogenous PGI2 in the blood.

O4F1024) - Comparison of canine isolated basilar and femoral arteries responses to ifenprodil tartrate.

O4F1024) - Comparison of canine isolated basilar and femoral arteries responses to ifenprodil tartrate.

A synthesis of DL‐erythro‐2‐(4‐benzylpiperidino)‐1‐(4‐hydroxyphenyl)‐[1‐14C]propan‐1‐OL L‐(+)‐tartrate

AbstractThe preparation of DL‐erythro‐2‐(4‐benzylpiperidino)‐1‐(4‐hydroxy‐phenyl)‐[1‐14C]propan‐1‐ol L‐(+)‐tartrate, Ifenprodil tartrate (Vadilex ®) from barium [14C]carbonate is described. The product was obtained in 29.2 % radiochemical yield and at a specifie activity of 47.6 mCi/mmol. This was diluted to 2 and 1 mCi/mmol for metabolism and distribution studies in man. The radiochemical purity of the diluted product exceeded 99 %.

Ifenprodil: Protective effect in experimental cyanide poisoning

In in vivo experiments, dose-dependent protection against the lethality of cyanide was elicited by im pretreatment with ifenprodil in rats, guinea pigs, rabbits, and mice. The decline in respiration rate, blood pressure, and heart rate, and the flat electroencephalogram induced by iv administration of sodium cyanide was also reversed by previous administration of ifenprodil in these species. Methemoglobinemia was not observed after protective doses of ifenprodil in rats and ifenprodil did not affect thiocyanate formation induced by sodium cyanide and sodium thiosulfate in rats. In vitro, ifenprodil exhibited a stimulative effect on respiration of mitochondria isolated from guinea-pig liver, this effect being the most prominent with succinate as substrate and in the presence of phosphate. In addition, the inhibitory effect of potassium cyanide on the respiration was completely abolished by ifenprodil. These protective effects of ifenprodil on cyanide intoxication were also observed with both ifenprodil tartrate and hydrochloride, and tartaric acid did not exert this action. Experiments using ultraviolet absorption and proton nuclear magnetic resonance spectra did not show that ifenprodil reacts directly with free cyanide ion to trap it. The results suggest that ifenprodil prevents the signs and lethality of cyanide, and a part of the mechanism can be ascribed to antagonism at the mitochondrial level, though the mechanism is not clear at present.