ABSTRACT
The aim of this study was to determine which of the muscarinic receptor subtypes are involved in the modulation of the urethrogenital reflex (UGR) in male, spinal cord-transected rats. The electromyographic (EMG) responses of the bulbospongiosus muscle (BS) to the topical spinal application of muscarine and the combination of muscarine and the selective muscarine receptor antagonists methoctramine (M2), AFDX (M2), 4DAMP (M3) and tropicamide (M4) were determined before and after the elicitation of UGR by way of the mechanical stimulation of the urethra. When 50- and 100-mug doses of muscarine were applied without urethral stimulation, a rhythmic activity of the BS was observed, similar to the one found when UGR was evoked. The M3 and M4 - but not the M2 - antagonists prevented BS response to muscarine when urethral stimulation was not performed. When UGR was elicited following urethral stimulation muscarine produced an increase in burst duration and a decrease in burst frequency. The M2 antagonist reverted the effects of muscarine on the UGR, while the M3 and M4 antagonists produced a significant increase in the frequency and in the bursts number, when compared to the control muscarine response. The differences observed in BS responses to muscarine and muscarine antagonists before and after UGR elicitation were probably linked to the intrinsic effects of the endogenous acethylcholine (Ach) released after urethral stimulation. The present results suggest a cholinergic modulation of UGR in spinal cord-transected rats mediated by the M2, M3 and M4 muscarinic receptor subtypes.
Subject(s)
Genitalia, Male/physiology , Receptors, Muscarinic/physiology , Reflex/physiology , Spinal Cord Injuries/physiopathology , Urethra/physiology , Animals , Dose-Response Relationship, Drug , Genitalia, Male/drug effects , Male , Muscarinic Agonists/pharmacology , Muscarinic Antagonists/pharmacology , Rats , Rats, Wistar , Reflex/drug effects , Sexual Behavior, Animal/drug effects , Sexual Behavior, Animal/physiology , Thoracic Vertebrae , Urethra/drug effectsABSTRACT
Se evaluó el perfil farmacocinético de HEPP debido a que diferentes estudios farmacodinámicos han mostrado amplio espectro de actividad anticonvulsionante y un bajo índice de neurotoxicidad. En este trabajo se describe la disposición de HEPP en ratas depués de la administración de un bolo intraperitoneal de 50 mg/kg, se obtuvieron muestras por punción cardiaca durante 16 h posteriores a la administración. Se analizó la concentración de HEPP por cromatografía de gases utilizando un método analítico desarrollado en nuestro laboratorio. El comportamiento cinético de este fármaco es bien definido por el modelo abierto bicompartamental y los principales parámetros farmacocinéticos son: vida media de absorción y eliminación (ty2) 0.05 y 2.3 h, respectivamante; concentración máxima (Cmáx) 50 µg/ml, tiempo de máxima concentración (t máx) 0.25 h; y tiempo medio de residencia en el organismo (TMR) 4.55 h. No se observó tiempo de lactancia
