Effects of atropine, pirenzepine, imipramine and phenothiazines on the mammalian neuromuscular junction.
1. Trifluoperazine (EC50 = 11.5 nM), chlorpromazine (13.8 microM), imipramine (15 microM), atropine (75.8 microM), and pirenzepine (316.2 microM), all produced neuromuscular facilitation and antagonized the blockade produced by oxotremorine (20 and 30 microM) in the rat isolated diaphragm. 2. These antagonists did not change the responses of curarized diaphragms to direct stimulation, or the twitch tension produced by retrograde injection of acetylcholine. 3. Trifluoperazine (2.5 ng, intra-arterially) reduced the tetanic fade produced by further intra-arterial injection of d-tubocurarine (10 micrograms/kg) in the in situ cat tibial muscle. 4. These results indicate that these antagonists may interact with muscarinic autoreceptors to increase acetylcholine output in the neuromuscular junction.
Alves-do-Prado
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Department of Pharmacology, Faculty of Medicine of Ribeirão Preto, SP, Brazil.
Corrado
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AP
Prado
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D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001285:Atropine / Q000494:pharmacology*; D003964:Diaphragm; D004558:Electric Stimulation; D005260:Female; D007099:Imipramine / Q000494:pharmacology*; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009469:Neuromuscular Junction / Q000187:drug effects* / Q000502:physiology; D010095:Oxotremorine / Q000037:antagonists & inhibitors; D010640:Phenothiazines / Q000494:pharmacology*; D010890:Pirenzepine / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011976:Receptors, Muscarinic / Q000378:metabolism; D014403:Tubocurarine / Q000037:antagonists & inhibitors
D010640:Phenothiazines; D011976:Receptors, Muscarinic; D010890:Pirenzepine; D010095:Oxotremorine; D001285:Atropine; D000109:Acetylcholine; D007099:Imipramine; D014403:Tubocurarine