Biomedical subjects

C K Kodama

Publications and source records attributed to C K Kodama.

5 recordsLinked to original sources

PubMed1988

Influence of D-1 receptor system on the D-2 receptor-mediated hypothermic response in mice.

The hypothermia induced by apomorphine, a mixed dopamine (DA) agonist in male Swiss-Webster mice, was not blocked by the selective D-1 antagonist SCH 23390 but was completely blocked by the selective D-2 antagonists haloperidol, sulpiride and YM-09151-2. The selective D-1 agonist SKF 38393 did not elicit hypothermic response but the selective D-2 agonist quinpirole caused a marked lowering of rectal temperature. D-2 antagonists blocked this response to quinpirole. SCH 23390 enhanced and SKF 38393 attenuated the hypothermia induced by quinpirole. Ineffective doses of haloperidol and SKF 38393, when given together, completely blocked the effect of quinpirole. It was concluded that hypothermia is a D-2 receptor mediated response but modulated by the D-1 receptor system. In another series of experiments the influence of neuroleptics and antidepressants on the hypothermic effect of apomorphine and quinpirole was investigated. The hypothermic effect of a low dose (1 mg/kg) of apomorphine was blocked by the D-2 receptor antagonists, but not by classical antidepressants. However, the response to a high dose (10 mg/kg) of apomorphine was blocked by both classical antidepressants and D-2 antagonists (except haloperidol). These drugs did not show similar effect on quinpirole-induced hypothermia. It is clear that the hypothermic response, especially that of quinpirole, is not a suitable model for testing either neuroleptics or antidepressants.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

PubMed1986

An in vivo pharmacological method for the quantitative evaluation of the central effects of alpha 1 adrenoceptor agonists and antagonists.

A new in vivo pharmacological method for the quantitative evaluation of alpha 1-adrenoceptor agonists and antagonists has been developed. It consists of recording the myoclonic twitch activity (MTA) of the suprahyoideal muscle of rats anesthetized with urethane. In these animals, the isomers of amphetamine elicited myoclonic twitch activity; their effects were dose-related and the d-isomer was approximately 3.5 times more effective than the l-isomer. While pimozide did not block this response, the postsynaptic alpha 1-antagonist prazosin fully blocked the myoclonic twitch activity induced by d-amphetamine. Other postsynaptic alpha 1-antagonists, such as haloperidol, phenoxybenzamine and clozapine, were also effective in blocking this response to d-amphetamine. Since d-amphetamine elicited myoclonic twitch activity in rats pretreated with reserpine and alpha-methyl-p-tyrosine, it was concluded that d-amphetamine exerted a direct alpha 1-adrenoceptor stimulation. In rats pretreated with nialamide and pimozide, l-DOPA elicited myoclonic twitch activity which was dose-related. This effect of l-DOPA was promptly and fully blocked by prazosin. It was concluded that this response to l-DOPA resulted from stimulation of alpha 1-adrenoceptors. The relative potencies of four alpha 1-adrenoceptor stimulants, namely, cirazoline, St-587, (-)SKF 89748A and Sgd 101/75 were determined using this method. The results correlated very well with their relative potencies to increase the diastolic blood pressure of pithed rats. Evidence that myoclonic twitch activity is a centrally-mediated response has also been presented. It appears that the method is a simple, sensitive, versatile and easily quantifiable procedure for the evaluation of the central effects of alpha 1-adrenoceptor agonists and antagonists.

Adrenergic alpha-Agonists↗

PubMed1985

Further studies on the ethanol antagonism exhibited by 2(2-chloro-5-trifluoromethyl phenylimino) imidazolidine (St 587).

A lipid soluble alpha 1-adrenoceptor agonist 2-(2-chloro-5-trifluoromethyl phenylimino) imidazolidine (St 587) dose-dependently antagonized the hypnotic, hypothermic and respiratory depressant effects of ethanol in C57B1/6 mice. This effect was present whether St 587 was given before or after ethanol. St 587 did not block the pentobarbitone-induced hypnosis. It also did not influence the elimination of ethanol. Combined treatment with a subhypnotic dose of ethanol and St 587 resulted in marked hyperactivity in mice. This effect was completely abolished by pimozide pretreatment. It was inferred that the dopamine released from brain areas by this dose of ethanol together with the norepinephrine receptor activation offered by St 587 resulted in this hyperactivity. Cirazoline, a more potent alpha 1-adrenoceptor agonist than St 587 was relatively more effective than the latter in blocking the ethanol-induced hypnosis in mice. It seems that alpha 1-adrenoceptor stimulation is a major contributing factor to the ethanol antagonism exerted by St 587. This drug might prove to be useful in the treatment of acute ethanol intoxication and in understanding the mode of action of ethanol.

Animals↗

PubMed1985

Antagonism of the hypnotic effect of ethanol in mice by an alpha-1 adrenoceptor agonist.

A lipid soluble alpha 1-adrenoceptor agonist 2-(2-chloro-5-trifluoromethylphenylimino) imidazolidine (St 587) antagonized the hypnotic effect of ethanol in C57Bl/6 and CD-1 mice. In Swiss-Webster mice the effect of St 587 was weak and in BALB/c mice this drug potentiated ethanol hypnosis. St 587 did not enhance the elimination of ethanol. Cirazoline, an alpha 1-adrenoceptor agonist which is more potent than St 587, was relatively more effective in antagonizing the ethanol-induced hypnosis. Though it appears that St 587 exerted its ethanol antagonism by virtue of its alpha 1-adrenoceptor agonistic effect, other contributing factors may also have to be considered. St 587 may prove to be of value in understanding the mechanism of action of ethanol and in the treatment of acute ethanol intoxication.

Adrenergic alpha-Agonists↗

PubMedDate not supplied

Studies on the interaction between ethanol and amfonelic acid.

Amfonelic acid (AFA), a non-amphetamine central stimulant dose-dependently reduced the hypnotic effect of ethanol in C57B1/6 mice. It did not enhance the elimination of ethanol. Amfonelic acid failed to modify the duration of pentobarbitone-induced hypnosis or the ethanol-induced hypothermia in these animals. Combined treatment with amfonelic acid and a lipophilic alpha 1-adrenoceptor agonist was not more effective than amfonelic acid alone in blocking ethanol hypnosis. The stimulation of locomotor activity by amfonelic acid in C57B1/6 mice was more sensitive to the blocking effect of ethanol than stimulation induced by d-amphetamine. The blocking effect of amfonelic acid, but not that of d-amphetamine, on the effects of ethanol developed tolerance. In pimozide-pretreated mice, amfonelic acid failed to reduce the ethanol-induced hypnosis. Hence it appears that dopamine (DA) released by amfonelic acid is responsible for its antagonism of ethanol. However, though amfonelic acid acted as a strong releaser of DA in Swiss-Webster, CD-1, DBA-2 and BALB/c mice, in these strains it failed to reduce the effect of ethanol. Moreover, methylphenidate, a dopaminergic stimulant, which acts by a mechanism similar to that of amfonelic acid was not effective in reducing the hypnotic effect of ethanol in C57B1/6 mice. For these reasons, additional mechanisms may have to be considered to explain this strain-dependent effect of amfonelic acid.

Animals↗