The a2 agonist B HT 933 was applied in doses of one ten mg kg i.m. to 4 animals handled with MPTP, and did not display any effect upon the parkinson like symptoms. With ten mg kg B HT 933, sedation and slight muscle relaxation were observed, lasting for a minimum of 2 h right after application. 4. Discussion The principle locating of our review is the fact that B HT 920, a identified a2 adrenoceptor and dopamine autoreceptor agonist, exerted a potent postsynaptic dopamine agonist activity in animals during which the postsynaptic brain dopamine receptors had been rendered supersensitive to dopamine.
As a result, B HT 920 strongly activated the locomotion in reserpine handled mice; was remarkably useful in creating contralateral rotation in rats using a 6 OH dopamine induced unilateral lesion within the ascending dopamine pathways for the forebrain; and antagonized the parkinson signs NVP-BGJ398 selleck chemicals in rhesus monkeys treated with parkinsonism inducing doses of MPTP. It truly is generally assumed that 83 below the above experimental circumstances, the postsynaptic brain dopamine receptors come to be supersensitive to dopamine . In contrast for the above pointed out agonist results of B HT 920 to the supersensitive postsynaptic dopamine receptors, when administered to naive rats, B HT 920, tested more than a broad dose range , diminished locomotor activity, was ineffective in creating apomorphine like stereotypies or ipsilateral turning in rats with unilateral lesions on the striatum, and, in doses as much as ten mg kg, did not block apomorphine induced stereotypies. These observations indicate that in rodents with normosensitive postsynaptic brain dopamine receptors, B HT 920 has no considerable agonist or antagonist postsynaptic activity. And6n et al.
implementing behavioral and biochemical criteria, have earlier characterized B HT 920 as a potent and selective dopamine autoreceptor agonist, a conclusion which explains satisfactorily our observations obtained in naive rodents. In contrast to apomorphine, B HT 920 did not reverse SB 203580 solubility the reserpine hypokinesia in mice when provided 4 h after reserpine. Based mostly on this reality, confirmed in our examine , And6n et al. excluded the likelihood of an apomorphine like postsynaptic dopamine agonist result of B HT 920. Yet, as proven in our experiments, B HT 920 had a potent anti reserpine impact in mice when offered 12 h or longer right after reserpine. Also in rats, B HT 920 had a clear reduce anti reserpine impact immediately after a few days of reserpine remedy ; when given 6 h following reserpine, only a peculiar state consisting of muscular twitching has become observed .