Possible Role for Acetylcholine as a Neurotransmitter in Canine Penile Erection

Stief, Christian G.; Diederichs, W.; Bénard, François; Bosch, Ruud; Aboseif, Sherif R.; Lue, Tom F.; Tanagho, Emil A.

doi:10.1159/000281540

Cited by 8 publications

(3 citation statements)

References 19 publications

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“…These results suggest that muscarinic receptor activation plays a significant role in mediating the erectile response to cavernosal nerve stimulation in the rat and that treatment with BAY 41‐8543 would be useful in situations where cholinergic nerve function is impaired. The present results are consistent with results in the literature showing that the erectile response to cavernosal nerve stimulation is reduced in the rat, dog and monkey by the administration of atropine [24–28]. Senbel et al.…”

Section: Discussionsupporting

confidence: 93%

Analysis of Erectile Responses to BAY 41-8543 and Muscarinic Receptor Stimulation in the Rat

Lasker

Pankey

Allain

et al. 2013

The Journal of Sexual Medicine

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Introduction Soluble guanylate cyclase (sGC) is the receptor for nitric oxide (NO) and in pathophysiologic conditions where NO formation or bioavailability is impaired, erectile dysfunction (ED) occurs. Aim The aim of this study was to investigate erectile responses to the sGC stimulator BAY 41-8543 in physiologic and pathophysiologic conditions. Methods Increases in intracavernosal pressure (ICP) in response to intracavernosal (ic) injections of BAY 41-8543 were investigated in the anesthetized rat. Main Outcome Measures Increases in ICP/MAP in response to ic injections of BAY 41-8543 and the interaction of BAY 41-8543 with exogenous and endogenously released NO were investigated and the effect of the sGC stimulator on cavernosal nerve injury was assessed. The mechanism of the increase in ICP/MAP in response to ic injection of acetylcholine was investigated. Results The ic injections of BAY 41-8543 increased ICP/MAP and the duration of the response. BAY 41-8543 was less potent than SNP and ic injections of BAY 41-8543 and SNP produced a larger response than the algebraic sum of responses to either agent alone. Simultaneous ic injection of BAY 41-8543 and cavernosal nerve stimulation produced a greater response than either intervention alone. Atropine and cavernosal nerve crush injury decreased the response to nerve stimulation and ic injection of BAY 41-8543 restored the response. Conclusion These data show that BAY 41-8543 has significant erectile activity and can synergize with exogenous and endogenously released NO. This study shows that atropine and nerve crush attenuate the response to cavernosal nerve stimulation and that BAY 41-8543 can restore the response. The results with atropine, L-NAME and hexamethonium indicate that the response to ic injection of acetylcholine is mediated by muscarinic receptors and the release of NO with no significant role for nicotinic receptors. These results suggest that BAY 41-8543 would be useful in the treatment of ED.

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Section: Discussionsupporting

confidence: 93%

Analysis of Erectile Responses to BAY 41-8543 and Muscarinic Receptor Stimulation in the Rat

Lasker

Pankey

Allain

et al. 2013

The Journal of Sexual Medicine

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“…This leads to direct stimulation of erection, as well as indirect action due to relaxation of the smooth muscles of the cavernous bodies and occlusion of the veins of the penis against the background of stimulation of NO-ergic synapses of cholinergic nerve fibers, as well as due to the vasodilating action of acetylcholine itself. 12,17,18 The effects of cholinesterase inhibitors on ED in various chronic conditions have not been intentionally assessed in clinical studies. Meanwhile, series of our experiments showed that ipidacrine may be successively used for recovery of sexual function in rats with spontaneously decreased one and for treatment of sexual activity disturbances associated with decreased secretion of sexual hormones and chronic stress.…”

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Ipidacrine (Axamon), A Reversible Cholinesterase Inhibitor, Improves Erectile Function in Male Rats With Diabetes Mellitus-Induced Erectile Dysfunction

Bykov

Gushchina²,

Morozov³

et al. 2022

Sexual Medicine

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Background: Management of diabetes mellitus-induced erectile dysfunction (DMED) is challenging because of its insufficient responses to phosphodiesterase type 5 inhibitors. Aim: To compare the effects of ipidacrine, a reversible cholinesterase inhibitor, and sildenafil on DMED in a rat model of streptozotocin (STZ)-induced diabetes. Methods: Erectile dysfunction (ED) caused by STZ-induced diabetes mellitus was modeled in adult male Wistar rats, which were randomized to 4 groups: untreated diabetic rats, sildenafil (5 mg/kg), ipidacrine (3.6 mg/kg) and ipidacrine (6.7 mg/kg). The test drug (ipidacrine), comparator (sildenafil) or control substance (1% starch solution) were administered orally for 5 days or 14 days. Erectile function was assessed by the change in the maximum intracavernous pressure (ICPmax) following cavernous nerve electrical stimulation. The mean arterial pressure (MAP) was recorded, and the ICPmax/MAP ratio was calculated. Sexual behavior, cholinesterase activity and blood testosterone level tests assessed. Main Outcome Measure: The quantitative value of ICPmax/MAP 14 days after the start of administration of the test drug and the comparison drug. Results: Animals with STZ-induced diabetes mellitus showed a significant decrease in ICPmax and ICPmax/ MAP ratio compared to the intact control group. When ipidacrine was administered to rats with DMED for 14 days, an increase in these indicators was noted. It was proved that ipidacrine at a dose of 6.7 mg/kg has noninferiority compared to sildenafil on the DMED model. Significant increase in ICPmax compared to STZ-control after electrostimulation of the cavernous nerve was recorded following administration of ipidacrine at a dose of 6.7 mg/kg (P < .05) and sildenafil at a dose 5 mg/kg (P < .05). Neither the test drug, nor the comparator were associated with increase in testosterone levels in blood; as well both drugs did not promote activation of sexual behavior. Clinical Implications: Ipidacrine may be considered as an effective therapy for DMED but needs to be verified in human investigations.Strengths & Limitations: The role of ipidacrine, was firstly demonstrated in rats with DMED. However, the results were obtained in animal experiments, and will be further tested in the study of receptor interactions and the determination of cellular targets. Conclusion: This is the first study to show that administration of ipidacrine, the reversible cholinesterase inhibitor, improved erectile function in diabetic rats and these results may be beneficial in further studies using ipidacrine for treatment of DMED, particularly in non-responders to PDE5 inhibitors.

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