Methoctramine and hexahydrodifenidol antagonise two muscarinic responses on the rat superior cervical ganglion with opposite selectivity.
Two novel muscarinic antagonists, methoctramine and hexahydrodifenidol, have been assessed for their action against two muscarinic agonist-induced responses on the rat superior cervical ganglion in vitro. DC recordings were made between the desheathed ganglion and its internal carotid nerve using the grease-gap technique. Hexahydrodifenidol and methoctramine antagonised the muscarine-induced M1-mediated depolarisation of this preparation with estimated pA2 values of 7.5 and 6.5, respectively. In 0.3 microM pirenzepine and 0.1 mM CaCl2, 1 microM muscarine evoked a hyperpolarisation mediated by cardiac-like M2 receptors. Hexahydrodifenidol and methoctramine antagonised this response with pIC50 values (-log10IC50) of 5.7 and 7.4, respectively. The selectivity of methoctramine for cardiac-like M2 receptors over M1 receptors is therefore confirmed and extended to these two neuronal responses. The selectivity of hexahydrodifenidol was opposite to, and greater than, that seen with methoctramine.
Merck Sharp and Dohme Research Laboratories, Neuroscience Research Centre, Harlow, U.K.
J L
JL
Field
N R
NR
Newberry
D000818:Animals; D003959:Diamines / Q000494:pharmacology*; D005728:Ganglia, Sympathetic / Q000187:drug effects / Q000502:physiology*; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009116:Muscarine / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000502:physiology*
D003959:Diamines; D010880:Piperidines; D011976:Receptors, Muscarinic; C060685:hexahydrodifenidol; D009116:Muscarine; C054938:methoctramine