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A Tobe

Publications and source records attributed to A Tobe.

44 records · Page 3Linked to original sources
PubMed1982

Selective potentiation of noradrenaline in the guinea-pig vas deferens by 2-(4-methylaminobutoxy) diphenylmethane hydrochloride (MCI-2016), a new psychotropic drug.

In the isolated vas deferens of the guinea-pig, the effects of 2-(4-methylaminobutoxy) diphenylmethane hydrochloride (MCI-2016), a new psychotropic drug, on the contractile response to various agonists or transmural electrical stimulation and on the release of noradrenaline (NA) from the tissue were examined and compared with cocaine. MCI-2016 (3 X 10(-6)M) and cocaine (3 X 10(-5)M) produced a leftward shift (15 and 20 times, respectively) of the dose-response curves for the contractile effect of NA and increased the maximum contractile response to NA by approximately 7 and 14% respectively. MCI-2016 had no apparent effect on the dose-response curves for methoxamine, acetylcholine and high K, while cocaine markedly shifted those for these agents to the left and increased the maximal responses (10, 16 and 16%, respectively). MCI-2016 and cocaine abolished the tyramine (3 X 10(-4)M)-induced contraction and inhibited the twitch response to transmural electrical stimulation in a dose-dependent manner. The inhibitory effects of both drugs on the twitch were reversed by yohimbine (10(-5)M). The spontaneous outflow of NA from the vas deferens was unaffected by MCI-2016 (3 X 10(-6)M) and cocaine (10(-5)M), while the high-K-evoked release of NA was increased by both drugs. In the presence of cocaine (10(-5)M), the high-K-evoked release of NA was markedly increased by yohimbine (10(-5)M) and decreased by clonidine (3 X 10(-8)M), but only slightly increased by MCI-2016 (3 X 10(-6)M). 7 In phaeochromocytoma cells, both MCI-2016 and cocaine at concentrations of 10-7 to 10-5 M caused a dose-dependent inhibition of the [3H]-NA uptake. 8 These results suggest that MCI-2016-induced supersensitivity is specific for NA and is due to interference with the neuronal uptake process for NA.

Animals↗
PubMed1981

Synthesis and antidepressant activity of substituted (omega-aminoalkoxy)benzene derivatives.

A series of substituted (omega-aminoalkoxy)benzene derivatives has been synthesized and screened for potential antidepressant activities. The effect of structural variation of these molecules has been systematically examined. Antidepressant activity was clearly displayed by 2-benzyl-1-[4-(methylamino)butoxy]benzene (7), 2-(2-hydroxybenzyl)-1-[4-(methylamino)butoxy]benzene (19), 1-[4-(methylamino)butoxy]-2-phenoxybenzene (29), and 1-[4-(methylamino)butoxy]-2-(phenylthio)benzene (31) in further pharmacological studies. These compounds did not possess the anticholinergic, antihistaminic, and muscle-relaxant side effects common to tricyclic antidepressants.

Amino Alcohols↗
PubMed1981

Pharmacological evaluation of 2-(4-methylaminobutoxy)diphenylmethane hydrochloride (MCI-2016), a new psychotropic drug with antidepressant activity.

Pharmacological properties of 2-(4-methylamino-butoxy)-diphenylmethane hydrochloride (MCI-2016) were examined in comparison with those of other antidepressants. MCI-2016 significantly antagonized the hypothermia and depression-like syndrome produced by reserpine injection. Furthermore, the drug exhibited such activities as antitetrabenazine and anti-cataleptic actions, and potentiation of the behavioural excitation induced by yohimbine, methamphetamine and L-dopa. MCI-2016 showed a definite suppressive effect on muricidal activity in olfactory bulb removed rats and the long-term isolation-induced fighting in mice without causing apparent motor disturbance. Judging from the effects of the drug on in vitro response to noradrenaline (NA) and serotonin (5-HT), and on p-chloramphetamine-induced hypermotility, it is suggested that MCI-2016 is a selective potentiator of NA presumably due to an inhibition of NA uptake. Anticholinergic and sedative actions of MCI-2016 were considerably weaker than those of amitriptyline and imipramine. Acute toxicity of MCI-2016 was the weakest among the drugs tested. These pharmacological profiles may suggest a potential clinical utility of MCI-2016 as a new psychotropic agent having an antidepressant activity.

Aggression↗
PubMed1976

Pharmacological studies on triazine derivatives V Sedative and neuroleptic actions of 2-amino-4-[4-(2-hydroxyethyl)-piperazin-1-yl]-6-trifluoromethyl-s-triazine (TR-10).

Pharmacological properties of 2 amino-4-[4-(2-hydroxyethyl)-piperazin-1-yl]-6-trifluoromethyl-s-triazine (TR-10) were investigated in mice and rats. Chlorpromazine served as a reference compound. Tr-10 expressed in general the pharmacological profiles as neuroleptic ascertained by anti-methamphetamine activity, supression of conditioned avoidance response, taming effects, decrease in exploratory behavior and cataleptogenic activity. Among these effects, anti-methamphetamine action was most potent. Different from chlorpromazine, TR-10 showed a similar pharmacological activity pattern in the intraperitoneal and oral routes of administration as depicted from ED50/LD50 values. Although the effects relevant to neuroleptics were less potent than chlorpromazine, such were seen with TR-10 at lower doses than those causing muscle relaxation. TR-10 significantly depressed the spontaneous motor activity but showed no anti-convulsant action in mice. Hypothermic action, potentiating effects of hypnotics and alpha-adrenergic blocking action, characteristic to chlorpromazine, were very weak for TR-10. TR-10 also showed low toxicity in mice (LD50 = 820 mg/kg p.o., 465 mg/kg i.p.) compared with that of chlorpromazine (LD50 = 370 mg/kg p.o., 228 mg/kg i.p.).

Acetates↗