Effects of two isomeric 1-aminoadamantanes on the membrane anisotropy and on alpha- and gamma-motoneurones excitability.
The structure-activity relationship of two isomeric 1-aminoadamantanes, 1-C-ethylaminoadamantane (D 174) and 1-amino-3-ethyladamantane (D 175), on membrane anisotropy and the excitability of neurons was studied in the CNS of the rat and in the decerebrated cat. Mass spectrometric analysis showed that after a single, 40 mg/kg dose, D 174 and D 175 were unevenly distributed within the CNS of the rat, moreover the distribution pattern of the two substances was different. As measured by fluorescence depolarization in controls the membrane anisotropy was found to be higher in the older parts as compared with the younger parts of the CNS. After i.p. application of 40 mg/kg the membrane anisotropy was reduced in the cortex by D 174, whereas D 174 and D 175 increased the rigidity in striatal membranes. If cortical membranes were incubated with the substances, the fluidizing effect of D 174 was more prominent than that of D 175. In the decerebrated cat only D 174 in a dose of 5 mg/kg i.p. raised the discharge of spinal alpha-motoneurones significantly. The results suggest that the membrane architecture is more affected by D 174 as compared with D 175 which is reflected by a greater effect on membrane anisotropy as well as on the activity of spinal alpha-motoneurones.
Max-Planck-Institute of Experimental Medicine, Department of Pharmacology, Göttingen, Federal Republic of Germany.
M
M
Melzacka
F
F
Block
W
W
Wesemann
G
G
Sturm
K H
KH
Sontag
D000218:Adamantane / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D008297:Male; D009046:Motor Neurons / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D013329:Structure-Activity Relationship
C061051:1-C-ethylaminoadamantane; C061052:1-amino-3-ethyladamantane; D000218:Adamantane