Effects of Antidepressant Drugs on Noradrenaline Accumulation and Contractile Responses in the Rat Anococcygeus Muscle

Woodruff

1978

Self Cite

1The ability of drugs to inhibit noradrenaline accumulation and to release noradrenaline was studied in the isolated anococcygeus muscle of the rat. 2 Noradrenaline, tyramine, 2-amino,6,7-dihydroxy-1,2,3,4-tetrahydronaphthalene (ADTN), 2-amino,6,7-dimethoxy-1,2,3,4-tetrahydronaphthalene (dimethyl ADTN), and 5-hydroxytryptamine were all potent inhibitors of noradrenaline accumulation and potent releasers of noradrenaline. ADTN was accumulated by the rat isolated anococcygeus muscle. 3 Amphetamine and desipramine were potent inhibitors of noradrenaline accumulation but poor releasers of noradrenaline. 4 Methoxamine, oxymetazoline, acetylcholine, and angiotensin were poor inhibitors of noradrenaline accumulation and did not release noradrenaline. 5 The mechanism of action of these drugs is discussed.

Section: Discussionmentioning

confidence: 99%

“…The accumulation of radioactivity in the rat anococcygeus muscle was measured as described by Doggrell & Woodruff (1977). Thus, rat isolated anococcygeus muscles, weighing 10-20 mg each, were mounted on wire frames under 0.2 to 0.5 g tension in 5 ml of Krebs solution, gassed with 95% 02 and 5% CO2.…”

Section: Methodsmentioning

confidence: 99%

Effects of Drugs on the Accumulation and Spontaneous Release of Noradrenaline in the Rat Anococcygeus Muscle

Woodruff

1978

Self Cite

“…Thus the excitatory and inhibitory responses to field stimulation were insensitive to both hexamethonium and atropine. In consequence, investigations which have used the rat anococcygeus muscle subsequently have been concerned either with aspects of noradrenergic transmission (e.g., Gibson & Gillespie, 1973;Gibson & Pollock, 1973;Gillespie & McGrath, 1974;Doggrell & Woodruff, 1977) or the nature of the inhibitory process (Gillespie & McGrath, 1973;Burnstock, Cocks & Crowe, 1978). 0007-1188/81/080829-07 $01.00…”

Section: Introductionmentioning

confidence: 99%

Effect of Antimuscarinic Agents on the Contractile Responses to Cholinomimetics in the Rat Anococcygeus Muscle

1981

The effects of antimuscarinic agents alone and in the presence of neostigmine on the contractile responses to exogenously applied cholinomimetics or (‐)‐noradrenaline were studied in the rat anococcygeus muscle. Atropine (1 × 10_9‐1 × 10−6m) alone, in the presence of hexamethonium (1 × 10−4m), or phentolamine (1 × 10−6m), inhibited responses to acetylcholine but not to (—)‐noradrenaline. The inhibitory effect with the higher concentrations of atropine (1 × 10−8— × 10−6m), was seen as an increase in the slopes of the concentration‐response curves. Atropine (1 × 10−8m) alone inhibited the responses to methacholine and carbachol without altering the slopes of the concentration‐response curves. Homatropine (1 × 10−6m) alone had no effect on responses to (‐)‐noradrenaline and inhibited responses to acetylcholine and methacholine. The inhibitory effect on responses to acetylcholine but not to methacholine, included an increase in the slopes of the concentration‐response curves. Neostigmine (1 × 10−6m) alone had no effect on responses to (—)‐noradrenaline and potentiated responses to acetylcholine and methacholine. The potentiating effect included an increase in the slopes of the concentration‐response curves. In the presence of neostigmine (1 × 10−6m), atropine (1times10−9m‐1times 10−6m) caused a parallel concentration‐dependent shift of the concentration‐response curves to acetylcholine. The pA2 values, in the presence of neostigmine, were independent of the concentration of atropine and of the agonist (acetylcholine, methacholine, or carbachol) used. In the presence of neostigmine (1 × 10−6m), homatropine (1 × 10−6m) also failed to alter the slopes of the concentration‐response curves to acetylcholine and was approximately 100 times less potent than atropine as an antimuscarinic agent. These results illustrate that, in the rat anococcygeus muscle, it is necessary to inhibit acetylcholinesterase before determining the relative potencies of antagonists at muscarinic receptors.

“…In this aspect it seems likely that mianserin is more potent than the tricyclic agents. High concentrations of the tricyclic antidepressants are necessary to antagonize the post-synaptic a-adrenoceptors (Sturmann, 1971;Doggrell & Woodruff, 1977). Similarly the relatively high potency mianserin has as an antagonist at presynaptic a-adrenoceptors is not shared by desipramine (Baumann & Maitre, 1977).…”

Section: Introductionmentioning

confidence: 99%

Effect of Mianserin on Noradrenergic Transmission in the Rat Anococcygeus Muscle

1980

The effects of mianserin on the accumulation of (−)‐[3H]‐noradrenaline and on contractile responses to field stimulation, exogenously applied (−)‐noradrenaline, and to tyramine were studied in the rat anococcygeus muscle. Mianserin (10−9to 10−5m) and nortriptyline (10−9to 10−5m) inhibited the accumulation of (−)‐[3H]‐noradrenaline. In this aspect mianserin had a similar potency to nortriptyline, the most potent tricyclic antidepressant in inhibiting noradrenaline accumulation in this tissue. Mianserin 10−9or 10−8m alone had no effect on contractile responses to field stimulation and to (−)‐noradrenaline but inhibited the responses to tyramine. The responses to field stimulation at low frequencies and to (−)‐noradrenaline were potentiated by 10−7and 10−6m mianserin. It is suggested that the inhibitory effect mianserin has on neuronal accumulation is primarily responsible for these effects. Mianserin 10−5m inhibited responses to field stimulation and to (−)‐noradrenaline. In the presence of nortriptyline (10−6m), the contractile responses to field stimulations were potentiated by mianserin (10−8, 10−7and 10−6m), 10−8m being the most potent in this aspect. Mianserin 10−8, 10−7, 10−6and 10−5m had a similar inhibitory effect on responses to (−)‐noradrenaline. In the absence of neuronal uptake, the potentiating effect of mianserin on responses to field stimulation may be due to antagonism at presynaptic α‐adrenoceptors. In the presence of 10−6m nortriptyline, 10−5m mianserin abolished responses to field stimulation. Following incubation of the tissue in the presence of 6‐hydroxydopamine (10−3m for 3 h), mianserin (10−7, 10−6and 10−5m) nortriptyline (10−7and 10−6m) and phentolamine (5 × 10−8and 5 × 10−7m) inhibited contractile responses to (−)‐noradrenaline. This illustrates the ability of these agents to inhibit the responses to noradrenaline at a postsynaptic site. The inhibitory effect was dose‐related with nortriptyline and phentolamine; this illustrates the ability of these agents to antagonize postsynaptic α‐adrenoceptors. The inhibitory effect observed with mianserin was not dose‐related. This suggests that in addition to its reported ability to antagonize postsynaptic α‐adrenoceptors, mianserin may have another post‐synaptic action at the level of, or distal to, the α‐adrenoceptor. These results illustrate that, in the rat anococcygeus muscle, mianserin is a potent inhibitor of noradrenaline accumulation and may be an antagonist at presynaptic α‐adrenoceptors. Mianserin also inhibits the responses to exogenously applied noradrenaline in this tissue by an action or actions at the level of, or distal to, the postsynaptic α‐adrenoceptor.