Effects of Some Phosphorylacetic Acid Hydrazides on Periferal Cholinegric Neurotransmission

Abstract

Cholinergic deficit has received considerable attention with respect to the development of therapeutic agents designed to ameliorate the cognitive symptomatology of the dementias. The influence of (2-chloroethoxy) (p-N,N- dimethylaminophenyl) phosphorylacetic acid hydrazide (CAPAH) and diphenylphosphorylacetic acid hydrazide (PHOSENAZID) on the processes of the synaptic transmission in the neuromuscular synapses of frog and rat was studied. Experiments revealed that the effectiveness of CAPAH was concentration- dependent: in low concentrations (10 - 100 nM) neuromuscular junction miniature end-plate currents (MEPC) were attenuated by 15 - 20 % (sensitising effect); at higher concentrations (0.1 mM) h4EPC amplitude was reduced. This effect was similar to that seen with blockers of the sodium channel component of the nicotinic receptor The HCI-salt of CAPAH also had a sensitising effect in low concentrations (1 - 10 nh4). By contrast, PHOSENAZID was not effective at low concentrations. These differences in the effects of CAPAH and PHOSENAZID on cholinergic neurotransmission appear dependent in changes in the phosphyl fragment of the molecule.