effect of agents acting on NMDA and dopamine receptors on the responses of phrenic nerve-diaphram preparations from aged rats

ABSTRACT

Alzheimer's Dementia [AD] and Parkinsonism are common in geriatric patients. The skeletal muscles are important in the proper function of aging animals and humans. This study focuses on the influence of memantine [used for moderate to severe AD] and levodopalcarbidopa [LDICD] [a corner stone in the treatment of Parkinsonism] on responses of isolated phrenic nerve-diaphragms [IPNDs] of aged male rats. From 100 aged male albino rats twenty were untreated to study in vitro effects of memantine and LD/CD on 1PNDs. Eighty rats were divided into Group-I [Control], Group II [oral meman tine, 1 .5mg/KgId], Group-Ill, [twice daily intraperitoneal LD/CD, 25/2.5mg/kg], Group-lV [both drugs]. After three weeks of treatment, animals were sacrificed; ten rats from each group were used to harvest IPNDs to study the effect of alIamine; 10 rats were used to measure nAchR [nicotinic acetyicholine receptor] alpha subunit mRNA by PCR. Heights of indirectly elicited contractions 63.1 +/- 4, 6. 41.5 +/- 4.5, 70.6 +/- 4.7, 53.9 +/- 3.3mm for Groups I through IV respectively, all differences were statistically significant K0.05]. Memantine treatment caused a leftward shift of sallamine log-concentration-response curve, LD/CD caused ri.htward shift. Reversal of neuromuscular block required ier neostigmine concentrations in the memantine group it smaller concentrations in the LD/CD group. In Vitro m.antine inhibited diaphragmatic responses to indirect stam1ation. Values of nAchR alpha subunit mRNA [micro g/dl] 1 +/- f116 [control], 0.13 +/- 0.11 [memnatine], 2.3 +/- 0.94 [LD/CD], 1.18 +/- 0.71 [both drugs] [p<0.05]. Memnatine inhibits neuromuscular transmission in vitro and with in vivo treatment. LD/CD treatment rtaaces neuiomuscular transmission. Clinical implications a1 further investigation