الفهرس 
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Abstract
SUMMARY
The present study was performed to study the possible effects of the antimicrobial drugs; sulphadimidine and cephradine on cholinergic transmission using; directly and indirectly stimulated rat phrenic nerve diaphragm preparation, transmurally stimulated guinea pig ileum and rabbit sciatic nerve-tibialis anterior muscle.
I-Effects on isolated preparation
a) Rat phrenic neroe - Hemidiaphragm prepamtion,
Both drugs significantly (P < 0.05) blocked the twitch responses of indirectly stimulated rat diaphragm.
Sulphadimidine (3. 6 and 8 mg/m}) evoked initial stimulatory effect of 22.3% ± 7.23, 13.08% ± 5.23 and 3% ± 0.72 respectively in the response at first minute that was followed by a blocking effect of 62.41% % ± 11.34, 81.18% ± 10.58 and 92.43% ± 6.76 respectively on the control twitch response after 15 minutes.
Cephradine (0.5, I and 2 mg/m}) induced a decrease in the control responses of 47.33% ± 6.49, 53.92% ± 3.04 and 79.28% ± 5.63 respectively, at the 30 th minutes.
Both drugs elicited a significant (P < 0.05 ) inhibition of the twitch responses of directly stimulated rat diaphragm.
Sulpadimidine (3, 6 and 8 mg/m!) induced an initial stimulatory effect in the first two minutes. Then evoked a blockage of the twitches of 65.54% ± 3.13, 71.39% ± 9.65 and 83.14% ± 8.46 respectively, after 30 minutes.
Cephradine (0.5, I and 2 mg/mD evoked a weak inhibition of the directly stimulated muscle re6ponses after 30 minutes.
(b) Effects on transmurally stimulated guinea pi/{ ileum :
The tested drugs significantly (P < 0.05) blocked the twitch
responses of transmurally stimulated guinea pig ileum preparation.
After 30 minutes, sulphadimidine (3, 6 and 8 mg/m!) induced 70.4% ± 5.34, 92.25% ± 5.36 and 98.56% ± 1.24 decrease in the control respons•es respectively. whereas, cephradine (0.5, I and 2 mg/ml) . evoked 23.16% ± 4.6, 25.4% ± 5.52 and 42.81% ± 5.74 blockade of the control twitch responses respectively.
Experiments conducted to disclose the possible site (s) of action of the tested drugs for inhibition of cholinergic transmission using isolated preparations, revealed that neostigmine failed to reverse the depressant effects of both drugs on indirectly stimulated rat diaphragm. Any possible interaction of both drugs with the presynaptic muscarinic receptors sites using the same preparation was excluded. Our results also revealed that there is no possible
interaction of both drugs with the presynaptic ~ receptors sites using
transmurally stimulated gUInea pIg ileum. Meanwhile, the inhibitory response of both drugs was ascribed via an interaction with calcium availability necessary for acetylcholine release mechanism(s).
Effect~ in intact animals:
The effects of both drugs on the intact animals were
investigated using the rabbit sciatic nerve-tibialis anterior muscle preparation. Sulphadimidine evoked a significant stimulation
115.44% ± 1.88) (P < 0.05) at adose level (360 mg/kg)
after 30 minutes. Meanwhile, cephradine produced a non significant inhibition of the control twitch responses by both therapeutic and double therapeutic doses
It could be concluded that both sulphadimidine and cephradine did induce a significant depressant effect on the central cholinergic transmission, at the neuromuscular junction in the isolated preparations; directly and indirectly stimulated rat diaphragm and transmurally stimulated guinea pig ileum.
Nevertheless, these results do not reflect any clinical significance as evident by lack of effects on intact animals.