Uroselective a 1A -blockers and finasteride are the primary drugs used for the pharmacotherapy of benign prostatic hyperplasia, which, like osteoporosis, develops with ageing in men. The aim of the study was to investigate the effect of a combination therapy (finasteride with tamsulosin or silodosin) on bone remodeling in rats with androgen deficiency induced by orchidectomy.Three-month-old Wistar rats were orchidectomized (ORX) or sham-operated, and, after 7 days, divided into 6 groups (n = 10): sham-operated control rats, ORX control rats, ORX rats receiving: tamsulosin, silodosin, finasteride and tamsulosin, or finasteride and silodosin. Tamsulosin (0.1 mg/kg), silodosin (0.3 mg/kg) and finasteride (1 mg/kg) were administered by a gastric tube once daily, for 9 weeks (6 days a week). Bone mass and mineral mass, calcium and phosphorus content in the bone mineral, histomorphometric parameters and mechanical properties of compact and cancellous bone were determined 10 weeks after ORX or sham operation.Orchidectomy-induced androgen deficiency intensified the resorption of cancellous and compact bone, resulting in significant decreases in the mass of bone mineral, calcium and phosphorus content, the cortical bone growth and transverse cross-section surface, width of trabeculae in the epiphysis and metaphysis of the femur, as well as significant worsening of mechanical properties of the tibial metaphysis and femoral diaphysis. The use of tamsulosin or silodosin counteracted the effects induced by androgen deficiency in cancellous and compact bone. The preventive effect of silodosin was stronger than that of tamsulosin, and finasteride weakened the effects of both drugs in trabecular bone.
http://dx.Orexin is apparently involved in some processes -metabolism, feeding, memory, sleep-wake cycle or nociception. Recently, an association between orexin-mediated events and seizure activity has been postulated. Blockade of orexin 1 receptors by N-(2-methyl-6benzoxazolyl)-N 0 -1,5-naphthyridin-4-yl urea (SB334867) resulted in an anticonvulsant effect against pentylenetetrazol-induced seizures in rats. Also, orexin A and B enhanced the convulsive potential of focal application of penicillin-G in rats. A question arises whether the orexin 1 receptor antagonist may affect the anticonvulsant efficacy of a number of antiepileptic drugs (AEDs). Experiments were conducted on male Swiss mice (20-24 g of weight) and seizure activity was induced by maximal electroshock (alternating current of 25 mA, stimulus duration of 0.2 s) delivered via ear electrodes. All drugs were given ip. Neurotoxic effects of AEDs combined with SB334867 were evaluated in the chimney test and passive avoidance task. SB334867 (0.625-1.25 mg/kg) did not affect the seizure threshold. When given at 1.25 mg/kg, SB334867 significantly impaired the anticonvulsant potential of two newer AEDs, lamotrigine and oxcarbazepine, increasing their ED50s from 3.6 to 7.1 and from 17.0 to 22.2 mg/kg, respectively. At 0.625 mg/kg, the orexin 1 receptor antagonist was ineffective...
