Delving into the Latest Updates on Carmoxirole with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

EMD 45609, EMD-45609

Target

D2 receptor

Mechanism

D2 receptor agonists(Dopamine D2 receptor agonists)

Therapeutic Areas

Cardiovascular Diseases

Active Indication-

Inactive Indication

Heart FailureHypertension

Originator Organization

Merck Serono SA

Active Organization-

Inactive Organization

Merck KGaAMerck Serono SA

Mitsubishi Tanabe Pharma Corp.

Drug Highest PhasePendingPhase 2

First Approval Date-

Regulation-

Login to view timeline

Structure

Molecular FormulaC24H27ClN2O2

InChIKeyLRJUHOBITQUXIO-UHFFFAOYSA-N

CAS Registry115092-85-8

We previously reported that the combination of the dopamine (DA) receptor agonist apomorphine and the 5-hydroxytryptamine (5-HT₂) receptor agonist m-chlorophenylpiperazine (m-CPP) in rats potently and selectively facilitates the ejaculatory response through activation of D₂-like and 5-HT_2C receptors, respectively.

AIM:

The aim of this study was to clarify the target level of the proejaculatory effects induced by combination of these agonists.

METHODS:

For in vivo behavioral studies, apomorphine and m-CPP were given intracerebroventricularly and intrathecally alone or in combination with either drug administered systemically. Male rats were acclimated to observational cages bedded in paper towels, and the occurrence of ex copula ejaculation was assessed by evaluating the presence and weight of ejaculatory plugs dropped from the tip of the penis to the paper towels or adhered to the tip of the penis at 30 min after drug administration. For in vitro contraction studies, seminal vesicles isolated from rats were suspended in an organ bath to test contractile responses to drug combinations, and the effects of the combined drugs on the contractile response of noradrenaline were also tested.

MAIN OUTCOME MEASURES:

The presence and weight of ejaculatory plugs produced by drug-induced ejaculation and the contractile responses of the seminal vesicle were evaluated.

RESULTS:

Intrathecal m-CPP (10 μg), but not intracerebroventricular m-CPP, evoked the synergistic effects on ejaculation when used in combination with systemically administered apomorphine (0.1 mg/kg, subcutaneous). Moreover, the synergy between m-CPP and apomorphine was completely abolished by the intrathecal 5-HT_2C receptor antagonist SB242084 (10 μg). Intrathecal or intracerebroventricular apomorphine (1-10 μg) evoked proejaculatory effects in combination with systemically administered m-CPP (0.3 mg/kg, intraperitoneal). The selective peripherally acting D₂-like receptor agonist carmoxirole did not evoke ejaculation when used in combination with m-CPP. Furthermore, isolated rat seminal vesicles were completely insensitive to the combination of apomorphine and m-CPP.

CONCLUSION:

These results indicated that the synergistic effects of the drugs on ejaculation were induced at the central level but not at peripheral sites. Our findings also suggested that the 5-HT_2C receptor mediated the stimulation of the spinal ejaculatory pattern generator and was synergistically potentiated by the spinal DA receptor and that activation of the supraspinal DA receptor was also involved in mediating these synergistic effects. Yoshizumi M, Yonezawa A, Kimura Y, et al. Central Mechanisms of Apomorphine and m-Chlorophenylpiperazine on Synergistic Action for Ejaculation in Rats. J Sex Med 2021;18:231-239.

01 Dec 2020·Pharmacological reports : PRQ4 · MEDICINE

The role of spinally located dopamine D2 receptors in the regulation of the blood glucose level in mice

Q4 · MEDICINE

Article

Author: Sim, YunBeom ; Lee, JinKoo ; Hong, JaeSeung ; Park, JungSeok ; Suh, HongWon ; Lee, HeeJung ; Feng, JingHui

BACKGROUND:

The possible role of dopamine D₂ receptors located in the spinal cord in the regulation of the blood glucose level have not been investigated before.

METHODS:

In the present study, the effect of D₂ receptor agonist and antagonist administered intrathecal (it) injection on the blood glucose level were examined in the Institute of Cancer Research (ICR) mice.

RESULTS:

We found that it injection with carmoxirole (D₂ receptor agonist) caused an elevation of the blood glucose level in a dose-dependent manner. Carmoxirole-induced increase of the blood glucose was significantly attenuated by L-741,626 (D₂ receptor antagonist). Previously, we indicated that intrathecal (it) treatment with 0.1 μg/5 μl pertussis toxin (PTX, a G_i/G_o inhibitor) produces a hypoglycemic effect in ICR in a long-term manner. In the present study, it pretreatment with PTX for 6 days almost abolished the hyperglycemic effect induced by carmoxirole. The plasma insulin level was elevated by carmoxirole, and L-741,626 or PTX pretreatment reduced carmoxirole-induced increment of the insulin level. In addition, the plasma corticosterone level was increased by carmoxirole but it pretreatment with L-741,626 or PTX did not affect carmoxirole-induced increment of the corticosterone level.

CONCLUSION:

Our results suggest that D₂ receptors located in the spinal cord play an important role in the elevation of the blood glucose level. Spinally located inhibitory G-proteins appear to be involved in hyperglycemic effect induced by carmoxirole.

01 Mar 2014·Respiratory physiology & neurobiologyQ4 · MEDICINE

Hypothyroidism affects D2 receptor-mediated breathing without altering D2 receptor expression

Q4 · MEDICINE

Article

Author: Del Rio, Rodrigo ; Schultz, Harold D ; Schlenker, Evelyn H

Bromocriptine depressed ventilation in air and D2 receptor expression in the nucleus tractus solitaries (NTS) in male hypothyroid hamsters. Here we postulated that in age-matched hypothyroid female hamsters, the pattern of D2 receptor modulation of breathing and D2 receptor expression would differ from those reported in hypothyroid males. In females hypothyroidism did not affect D2 receptor protein levels in the NTS, carotid bodies or striatum. Bromocriptine, but not carmoxirole (a peripheral D2 receptor agonist), increased oxygen consumption and body temperature in awake air-exposed hypothyroid female hamsters and stimulated their ventilation before and following exposure to hypoxia. Carmoxirole depressed frequency of breathing in euthyroid hamsters prior to, during and following hypoxia exposures and stimulated it in the hypothyroid hamsters following hypoxia. Although hypothyroidism did not affect expression of D2 receptors, it influenced central D2 modulation of breathing in a disparate manner relative to euthyroid hamsters.

100 Deals associated with Carmoxirole

Login to view more data