manassantin-a and Blepharoptosis

In an earlier preliminary study, manassantin A, a neolignoid from Saururus cernuus was found to show neuroleptic type activity in mice when given by the i.p. route. It blocked the stereotypy and hyperactivity caused by amphetamine at doses comparable to those of haloperidol, but unlike the latter, did not show catalepsy or ptosis at atoxic doses. In the present study, a more detailed comparison of manassantin A with haloperidol and in some cases with chlorpromazine and reserpine using a variety of neuroleptic parameters and by various routes of administration is described. Results of the present study clearly show that the drug is readily absorbed from various routes of administration and shows many of the patterns of neuroleptic activity. Manassantin A was comparable to haloperidol in many of the tests but unlike the latter, did not produce antiadrenergic or anticholinergic effects. Manassantin A was found to bind weakly to calf caudate membranes (IC50 3500 nM) while haloperidol (IC50 5 nM) and chlorpromazine (IC50 50 nM) inhibited [3H]haloperidol binding. Manassantin A also did not affect the dopamine-induced adenylate cyclase activity in rat caudate nuclei (IC50 greater than 10,000 nM) while haloperidol (IC50 700 nM) and chlorpromazine (IC50 350 nM) inhibited the enzyme synthesis. These biochemical and behavioral tests suggest that manassantin A exhibits a selective neuroleptic profile and may be considered to behave as an atypical agent.

Topics: Adenylyl Cyclase Inhibitors; Amphetamine; Animals; Antipsychotic Agents; Behavior, Animal; Binding, Competitive; Blepharoptosis; Body Temperature; Catalepsy; Furans; Haloperidol; In Vitro Techniques; Levodopa; Lignans; Male; Mice; Norepinephrine; Pentobarbital; Physostigmine; Plants, Medicinal; Stereotyped Behavior

Manassantin A (MNS-A), a novel dineolignan isolated from Saururus cernuus was evaluated for its central depressant effects. Intraperitoneal (IP) administration of MNS-A to mice at nontoxic doses caused a decrease in spontaneous motor activity and inhibition of amphetamine-induced stereotypy, with an ED50 of 0.21 +/- 0.02 mg/kg for its antiamphetamine activity. Doses of MNS-A up to the LD50 did not produce catalepsy and ptosis as were observed with haloperidol used as a reference drug. The compound caused a dose-dependent hypothermia, while haloperidol was not very effective in this test. Potentiation of pentobarbital-sleeping time was observed to be of comparable degree with both drugs. In spite of the higher toxicity (acute LD50 5.4 +/- 0.2 mg/kg, IP) than that shown by haloperidol, the somewhat selective neuroleptic profile of MNS-A makes it an interesting candidate for more detailed studies.

Topics: Amphetamine; Animals; Antipsychotic Agents; Blepharoptosis; Body Temperature; Catalepsy; Furans; Haloperidol; Lignans; Mice; Motor Activity; Plants, Medicinal; Rats; Sleep; Stereotyped Behavior