The effect of memantine and levodopa/carbidopa on the responses of phrenic nerve-diaphragm preparations from aged rats.
BACKGROUND
Alzheimer's dementia (AD) and Parkinsonism are common in geriatric patients. Skeletal muscles are important for proper function of aging animals and humans. This study focuses on the influence of memantine (used in moderate to severe AD) and levodopa/carbidopa (LD/CD) (a cornerstone of Parkinson's disease treatment) on responses of isolated phrenic nerve-diaphragms (IPNDs) of aged male rats.


METHODS
Of 100 aged male albino rats, 20 were untreated to study the in vitro effects of memantine and LD/CD on IPNDs and 80 were divided into groups 1 (control), 2 (oral memantine, 1.5 mg/kg/d), 3 (twice daily intraperitoneal LD/CD, 25/2.5 mg/kg), and 4 (both drugs). After three weeks-treatment the animals were sacrificed. Ten rats from each group were used to harvest IPNDs to study the effect of gallamine and 10 rats to measure nAchR (nicotinic acetylcholine receptor) alpha subunit mRNA by PCR.


RESULTS
The heights of indirectly elicited contractions were 63.1+/-4.6, 41.5+/-4.5, 70.6+/-4.7, and 53.9+/-3.3 mm for groups 1-4, respectively, and all differences were statistically significant (p<0.05). Memantine caused a leftward shift of the gallamine concentration-response curve and LD/CD a rightward shift. Reversal of neuromuscular block required larger neostigmine concentrations in the memantine group and smaller concentrations in the LD/CD group. In vitro, memantine inhibited diaphragmatic responses to indirect stimulation. Values of nAchR alpha subunit mRNA (microg/dl) were 0.7+/-0.16 (control), 0.13+/-0.11 (memantine), 2.3+/-0.94 (LD/CD), and 1.18+/-0.71 (both drugs) (p<0.05).


CONCLUSIONS
Memantine inhibits neuromuscular transmission in vitro and with in vivo treatment. LD/CD treatment enhances neuromuscular transmission. Clinical implications need further investigation.
Department of Clinical Pharmacology, Faculty of Medicine, Cairo University, Cairo, Egypt. sohaelmoursy69@hotmail.com
Soha Ali
SA
El-Moursy
Heba M
HM
Shawky
Zainab
Z
Abdel Wahab
Laila
L
Rashed
D000375:Aging / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D002230:Carbidopa / Q000494:pharmacology*; D003964:Diaphragm / Q000187:drug effects* / Q000502:physiology; D004558:Electric Stimulation; D005703:Gallamine Triethiodide / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D007980:Levodopa / Q000494:pharmacology*; D008297:Male; D008559:Memantine / Q000494:pharmacology*; D009119:Muscle Contraction / Q000187:drug effects; D009388:Neostigmine / Q000494:pharmacology; D019148:Neuromuscular Blockade; D010791:Phrenic Nerve / Q000187:drug effects* / Q000502:physiology; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011978:Receptors, Nicotinic / Q000235:genetics / Q000378:metabolism
D021122:Protein Subunits; D012333:RNA, Messenger; D011978:Receptors, Nicotinic; D009388:Neostigmine; D007980:Levodopa; D002230:Carbidopa; D005703:Gallamine Triethiodide; D008559:Memantine